Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-cphqk Total loading time: 0 Render date: 2025-02-10T14:52:03.920Z Has data issue: false hasContentIssue false

3 - The microenvironment in health and cancer of the mammary gland

Published online by Cambridge University Press:  16 May 2011

By
John P. Wiebe
Edited by
C. G. Nicholas Mascie-Taylor  and
Lyliane Rosetta
John P. Wiebe
Affiliation:
University of Western Ontario, Canada
C. G. Nicholas Mascie-Taylor
Affiliation:
University of Cambridge
Lyliane Rosetta
Affiliation:
Centre National de la Recherche Scientifique (CNRS), Paris
Get access

Summary

Introduction

Mammary glands do not normally feature prominently in discussions of reproduction. Instead, discussions of reproduction deservedly emphasize the primary sex organs, the reproductive tract and the cardinal hormones (gonadotrophins and gonadal steroids) involved. However, newborn mammals cannot process foraged food and only the mammary gland is capable of synthesizing renewable food, in the form of milk, which is digestible by the neonates. Milk is a complex nutrient, consisting mainly of milk sugar (lactose), lipids, the milk proteins (casein and whey) as well as monovalent and divalent cations and immune antibodies. The female mammary glands are markedly altered functionally and morphologically during pregnancy in preparation for the production of this complex liquid food mixture for delivery to the neonates. The mammary gland thus forms an important adjunct to the mammalian reproductive system and is essential for the survival of mammalian species.

The conversion from inactive to active milk-producing mammary tissues requires extensive surges in cell proliferation as well as metabolic modifications. These alterations occur regularly during each ovulatory cycle in preparation for a potential pregnancy and the post-partum lactational activity.

In the absence of pregnancy, the proliferative rate returns to basal levels in the normal breast. The regulation of these proliferative oscillations depends on the steroid hormone milieu within microregions of the breast. It is argued that dysregulation of this microenvironment can lead to conditions within regions of the breast that result in foci of neoplasia.

Type
Chapter
Information
Reproduction and Adaptation
Topics in Human Reproductive Ecology
 , pp. 50 - 79
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ahamed, S., Foster, J.S., Bukovsky, A. & Wimalasena, J. (2001). Signal transduction through the ras/erk pathway is essential for the mycoestrogen zearalenone-induced cell-cycle progression in MCF-7 cells. Molecular Carcinogenesis, 30, 88–98.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Anderson, T.J., Battersby, S., King, R.J.B., McPherson, K. & Going, J.J. (1989). Oral contraceptive use influences resting breast proliferation. Human Pathology, 20, 1139–44.CrossRefGoogle ScholarPubMed
Anderson, W.A., Perotti, M.E., McManaway, M., Lindsey, S. & Eckberg, W.R. (1984). Similarities and differences in the ultrastructure of two hormone- dependent and one independent human breast carcinoma grown in athymic nude mice: comparison with the rat DMBA-induced tumor and normal secretory mammocytes. Journal of Submicroscopic Cytology, 16, 673–90.Google ScholarPubMed
Bakken, K., Alsaker, E., Eggen, A.E. & Lund, E. (2004). Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study. International Journal of Cancer, 112, 130–4.CrossRefGoogle ScholarPubMed
Bauer, E.R., Daxenberger, A., Petri, T., Sauerwein, H. & Meyer, H.H. (2000). Characterization of the affinity of different anabolic and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor. Acta Pathologica, Microbiologica, et Immunologica Scandinavica, 108, 838–46.CrossRefGoogle Scholar
Baulieu, E.-E. (1990). Hormones: a complex communication network. In Hormones: From Molecules to Diseases, ed. Baulieu, E-E. & Kelly, P.A.. Paris: Hermann, pp. 38.Google Scholar
Ben-Ze'ev, A. (1985). The cytoskeleton in cancer cells. Biochimica et Biophysica Acta, 780, 197–212.Google ScholarPubMed
Beral, V. & Million Women Study Collaborators. (2003). Breast cancer and hormone replacement therapy in the Million Women Study. Lancet, 362, 419–27.CrossRefGoogle ScholarPubMed
Bershadsky, A.D., Gluck, U., Denisenko, O.N., Sklyarova, T.V.et al. (1995). The state of actin assembly regulates actin and vinculin expression by a feedback loop. Journal of Cell Science, 108, 183–93.Google ScholarPubMed
Boudreau, N. & Myers, C. (2003). Breast cancer-induced angiogenesis: multiple mechanisms and the role of the microenvironment. Breast Cancer Research, 5, 140–6.CrossRefGoogle ScholarPubMed
Braunsberg, H., Coldham, N.G., Leake, R.E., Cowan, S.K. & Wong, W.R. (1987). Action of a progestogen on human breast cancer cells: mechanism of growth stimulation and inhibition. European Journal of Cancer and Clinical Oncology, 23, 563–72.CrossRefGoogle Scholar
Bulbrook, R.D., Moore, J.W., Clark, G.M.et al. (1986). Relation between risk of breast cancer and biological availability of estradiol in the blood: prospective study in Guernsey. Annals of the New York Academy of Sciences, 464, 378–88.CrossRefGoogle ScholarPubMed
Cappelletti, V., Ruedl, C., Granata, G.et al. (1991). Interaction between hormone-dependent and hormone-independent human breast cancer cells. European Journal of Cancer, 27, 1154–7.CrossRefGoogle ScholarPubMed
Castro-Rivera, E., Samudio, I. & Safe, S. (2001). Estrogen regulation of cyclin D1 gene expression in ZR-75 breast cancer cells involves multiple enhancer elements. The Journal of Biological Chemistry, 276, 30853–61.CrossRefGoogle ScholarPubMed
Cauley, J.A., Lucas, F.L., Kuller, L.H.et al. (1999). Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Annals of Internal Medicine, 130, 270–7.CrossRefGoogle ScholarPubMed
Chambers, A.F., Groom, A.C. & MacDonald, I.C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nature Reviews. Cancer, 2, 563–73.CrossRefGoogle ScholarPubMed
Chatterton, R.T.., Geiger, A.S., Gann, P.H. & Khan, S.A. (2003). Formation of estrone and estradiol from estrone sulfate by normal breast parenchymal tissue. Journal of Steroid Biochemistry and Molecular Biology, 86, 159–66.CrossRefGoogle ScholarPubMed
Chatterton, R.T.., Geiger, A.S., Khan, S.A.et al. (2004). Variation in estradiol, estradiol precursors, and estrogen-related products in nipple aspirate fluid from normal premenopausal women. Cancer Epidemiology, Biomarkers and Prevention, 13, 928–35.Google ScholarPubMed
Chatterton, R.T.., Geiger, A.S., Mateo, E.T., Helenowski, I.B. & Gann, P.H. (2005). Comparison of hormone levels in nipple aspirate fluid of pre- and postmenopausal women: effect of oral contraceptives and hormone replacement. Journal of Clinical Endocrinology and Metabolism, 90, 1686–91.CrossRefGoogle ScholarPubMed
Chlebowski, R.T., Hendrix, S.L., Langer, R.D.et al. (2003). Influence of oestrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Randomized Trial. Journal of the American Medical Association, 289, 3243–53.CrossRefGoogle ScholarPubMed
Clark, C.L. & Sutherland, R.L. (1990). Progestin regulation of cellular proliferation. Endocrine Reviews, 11, 266–302.CrossRefGoogle Scholar
Clark, R., Skaar, T., Baumann, K.et al. (1994). Hormonal carcinogenesis in breast cancer: cellular and molecular studies of malignant progression. Breast Cancer Research and Treatment, 31, 237–48.CrossRefGoogle Scholar
Cohen, S.M. & Ellwein, L.B. (1990). Cell proliferation in carcinogenesis. Science, 249, 1007–11.CrossRefGoogle ScholarPubMed
Daxenberger, A., Meyer, K., Hageleit, M. & Meyer, H.H.D. (1999). Detection of melengestrol acetate residues in plasma and edible tissues of heifers. Veterinary Quarterly, 21, 154–8.CrossRefGoogle ScholarPubMed
Duan, J., Dai, S., Fang, C.X.et al. (2006). Phytoestrogen α-zearalanol antagonizes homocysteine-induced imbalance of nitric oxide/endothelin-1 and apoptosis in human umbilical vein endothelial cells. Cell Biochemistry and Biophysics, 45, 137–45.CrossRefGoogle ScholarPubMed
Edel, M.J., Harvey, J.M. & Papadimitriou, J.M. (2000). Comparison of vascularity and angiogenesis in primary invasive mammary carcinomas and in their respective axillary lymph node metastases. Clinical and Experimental Metastasis, 18, 695–702.CrossRefGoogle ScholarPubMed
Eechaute, W., Thibault de Boesinghe, L. & Lacroix, E. (1983). Steroid metabolism and steroid receptors in methylbenz(a)anthracene-induced rat mammary tumors. Cancer Research 43, 4260–5.Google Scholar
,EFSA (2007). Opinion of the Scientific Panel on contaminants in the food chain on a request from the Commission related to hormone residues in bovine meat and meat products. Adopted on 12 June, 2007. The EFSA Journal, 510, 1–62. (www.efsa.europa.eu)Google Scholar
Eliasson, A.H., Missmer, S.A., Tworoger, S.S.et al. (2006). Endogenous steroid hormone concentrations and risk of breast cancer among postmenopausal women. Journal of the National Cancer Institute, 98, 1406–15.CrossRefGoogle Scholar
Fennessey, P.V., Pike, A.W., Gonzalez-Aller, C. & Horwitz, K.B. (1986). Progesterone metabolism in T47Dco human breast cancer cells–I. 5α-pregnan-3β,6α-diol-20-one is the secreted product. Journal of Steroid Biochemistry, 25, 641–8.CrossRefGoogle Scholar
Foster, J.S. & Wimalasena, J. (1996). Estrogen regulates activity of cyclin-dependent kinases and retinoblastoma protein phosphorylation in breast cancer cells. Molecular Endocrinology, 10, 488–98.Google ScholarPubMed
Fotherby, K. (1996). Bioavailability of orally administered sex steroids used in oral contraception and hormone replacement therapy. Contraception, 54, 59–69.CrossRefGoogle ScholarPubMed
Fournier, A., Berrino, F., Riboli, E., Avenel, V. & Clavel-Chapelon, F. (2005). Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. International Journal of Cancer, 114, 448–54.CrossRefGoogle ScholarPubMed
Galbraith, H. (2002). Hormones in international meat production: biological, sociological and consumer issues. Nutrition Research Reviews, 15, 243–314.CrossRefGoogle ScholarPubMed
Gann, P.H., Geiger, A.S., Helenowski, I.B., Vonesh, E.F. & Chatterton, R.T. (2006). Estrogen and progesterone levels in nipple aspirate fluid of healthy premenopausal women: relationship to steroid precursors and response proteins. Cancer Epidemiology, Biomarkers and Prevention, 15, 39–44.CrossRefGoogle ScholarPubMed
Garland, C.F., Friedlander, N.J., Barrett-Connor, E. & Khaw, K.T. (1992). Sex hormones and postmenopausal breast cancer: a prospective study in an adult community. American Journal of Epidemiology, 135, 1220–30.CrossRefGoogle Scholar
Going, J.J., Anderson, T.J., Battersby, S. & MacIntyre, C.C.A. (1988). Proliferative and secretory activity in human breast during natural and artificial menstrual cycles. American Journal of Pathology, 130, 193–204.Google ScholarPubMed
Groshong, S.D., Owen, G. I., Grimison, B.et al. (1997). Biphasic regulation of breast cancer cell growth by progesterone: role of the cyclin-dependent kinase inhibitors, p21 and p27Kip1. Molecular Endocrinology, 11, 1593–607.CrossRefGoogle Scholar
Gumbiner, B.M. (1996). Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell, 84, 345–57.CrossRefGoogle ScholarPubMed
Hageleit, M., Daxenberger, A. & Meyer, H.H.D. (2001). A sensitive enzyme immunoassay (EIA) for the determination of melengestrol acetate (MGA) in adipose and muscle tissues. Food Additives and Contaminants, 18, 285–91.CrossRefGoogle ScholarPubMed
Hankinson, S.E., Willett, W.C., Manson, J.E.et al. (1998). Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. Journal of the National Cancer Institute, 90, 1292–9.CrossRefGoogle ScholarPubMed
Helzlsouer, K.J., Alberg, A.J., Bush, T.L.et al. (1994). A prospective study of endogenous hormones and breast cancer. Cancer Detection and Prevention, 18, 79–85.Google ScholarPubMed
Henricks, D.M., Gray, S.L., Owenby, J.J. & Lackey, B.R. (2001). Residues from anabolic preparations after good veterinary practice. Acta Pathologica, Microbiologica et Immunologica Scandinavica, 109, S345–55.CrossRefGoogle ScholarPubMed
Henzl, M.R. (2001). Norgestimate. From the laboratory to three clinical indications. The Journal of Reproductive Medicine, 46, 647–61.Google Scholar
Horwitz, K.B., Costlow, M.E. & McGuire, W.L. (1975). MCF-7: a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. Steroids, 26, 785–95.CrossRefGoogle ScholarPubMed
Horwitz, K.B., Pike, A.W., Gonzalez-Aller, C. & Fennessey, P.V. (1986). Progesterone metabolism in T47Dco human breast cancer cells–II. Intracellular metabolic path of progesterone and synthetic progestins. Journal of Steroid Biochemistry, 25, 911–6.CrossRefGoogle ScholarPubMed
Horwitz, K.B., Wei, L.L., Sedlacek, S.M. & D'Arville, C.N. (1985). Progestin action and progesterone receptor structure in human breast cancer: a review. Recent Progress in Hormone Research, 41, 249–316.Google ScholarPubMed
Humphries, M.J. & Newham, P. (1998). The structure of cell-adhesion molecules. Trends in Cell Biology, 8, 78–83.CrossRefGoogle ScholarPubMed
Irshaid, F., Kulp, S.K., Sugimoto, Y., Lee, K. & Lin, Y.C. (1999). Zeranol stimulates estrogen-regulated gene expression on MCF-7 human breast cancer cells and normal human breast epithelial cells. Biology of Reproduction, 60 (Suppl. 1), 234–5.Google Scholar
Jabara, A.G. (1967). Effects of progesterone on 9,10-dimethyl-1,2-benzanthracene-induced mammary tumours in Sprague-Dawley rats. British Journal of Cancer, 21, 418–29.CrossRefGoogle ScholarPubMed
Jernstrom, H., Bendhal, P.O., Lidfeldt, J.et al. (2003). A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden). Cancer Causes and Control, 14, 673–80.CrossRefGoogle Scholar
Kaaks, R., Berrino, F., Key, T.et al. (2005). Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). Journal of the National Cancer Institute, 97, 755–65.CrossRefGoogle Scholar
Kabuto, M., Akiba, S., Stevens, R.G., Neriishi, K. & Land, C.E. (2000). A prospective study of estradiol and breast cancer in Japanese women. Cancer Epidemiology, Biomarkers and Prevention, 9, 575–9.Google ScholarPubMed
King, R.J.B. (1991). A discussion of the roles of estrogen and progestin in human mammary carcinogenesis. Journal of Steroid Biochemistry and Molecular Biology, 39, 811–18.CrossRefGoogle ScholarPubMed
Lanari, C. & Molinolo, A.A. (2002). Progesterone receptors – animal models and cell signaling in breast cancer. Diverse activation pathways for the progesterone receptor: possible implications for breast biology and cancer. Breast Cancer Research, 4, 240–3.CrossRefGoogle ScholarPubMed
Guevel, R. & Pakdel, F. (2001). Assessment of oestrogenic potency of chemicals used as growth promoter by in-vitro methods. Human Reproduction, 16, 1030–6.CrossRefGoogle ScholarPubMed
Lenton, E.A., Landgren, B.M. & Sexton, L. (1984a). Normal variation in the length of the luteal phase of menstrual cycle: identification of the short luteal phase. British Journal of Obstetrics and Gynaecology, 91, 685–9.CrossRefGoogle ScholarPubMed
Lenton, E.A., Landgren, B.M., Sexton, L. & Harper, R. (1984b). Normal variation in the length of the follicular phase of the menstrual cycle: effect of chronological age. British Journal of Obstetrics and Gynaecology, 91, 681–4.CrossRefGoogle ScholarPubMed
Leung, B.S., Sasaki, G.H. & Leung, J.S. (1975). Estrogen-prolactin dependency in 7, 12-dimethylbenz(a) anthracene-induced tumors. Cancer Research, 35, 621–7.Google ScholarPubMed
Lewis, M.J., Wiebe, J.P. & Heathcote, J.G. (2004). Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma. BMC Cancer, 4,(27), 1–12. (http://www.biomedcentral.com/1471–2407/4/27.)CrossRefGoogle ScholarPubMed
Li, C.I., Malone, K.E., Porter, P.L.et al. (2003). Relationship between long durations and different regimens of hormone therapy and risk of breast cancer. Journal of the American Medical Association, 289, 3254–63.CrossRefGoogle ScholarPubMed
Lin, Y.C., Kulp, S.K., Sugimoto, Y. & Brueggemeier, R.W. (2000). Potential risk of growth promoter in beef for breast cancer growth. Era of Hope, Department of Defence Breast Cancer Research Program Meeting Proceedings 2000 II, 480.Google Scholar
Liu, S. & Lin, Y.C. (2004). Transformation of MCF-10A human breast epithelial cells by zeranol and estradiol-17beta. Breast Journal, 10, 514–21.CrossRefGoogle ScholarPubMed
Liu, S., Sugimoto, Y., Sorio, C., Tecchio, C. & Lin, Y.C. (2004). Function analysis of estrogenically regulated protein tyrosine phosphatase γ (PTPγ) in human breast cancer cell line MCF-7. Oncogene, 23, 1256–62.CrossRefGoogle Scholar
Lloyd, R.V. (1979). Studies on the progesterone receptor content and steroid metabolism in normal and pathological human breast tissues. Journal of Clinical Endocrinology and Metabolism, 48, 585–93.CrossRefGoogle ScholarPubMed
Luo, S., Stojanovic, M. & Labrie, F. (1997). Inhibitory effect of the novel anti-estrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthracene-induced mammary carcinoma in rats. International Journal of Cancer, 73, 580–6.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Lyons, W.R., Li, C.H. & Johnson, R.E. (1958). The hormonal control of mammary growth and lactation. Recent Progress in Hormone Research, 14, 219–54.Google ScholarPubMed
MacNeil, J.D., Reid, J., Neiser, C.D. & Fesser, A.C.E. (2003). Single-laboratory validation of a modified liquid chromatographic method with UV detection for determination of trenbolone residues in bovine liver and muscle. Journal of the AOAC International, 86, 916–24.Google Scholar
Manjer, J., Johansson, R., Berglund, G.et al. (2003). Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin and SHBG (Sweden). Cancer Causes and Control, 14, 599–607.CrossRefGoogle Scholar
Martin, P.M., Horwitz, K.B., Ryan, D.S. & McGuire, W.L. (1978). Phytoestrogen interaction with estrogen receptors in human breast cancer cells. Endocrinology, 103, 1860–7.CrossRefGoogle ScholarPubMed
Milgrom, E. (1990). Steroid hormones. In Hormones: From Molecules to Diseases, ed. Baulieu, E-E. and Kelly, P.A.. Paris: Hermann, pp. 425.Google Scholar
Miller, W.R. (1990). Pathways of hormone metabolism in normal and non-neoplastic breast tissue. Annals of the New York Academy of Sciences, 586, 53–59.CrossRefGoogle Scholar
Missmer, S.A., Eliassen, A.H., Barbieri, R.L. & Hankinson, S.E. (2004). Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. Journal of the National Cancer Institute, 96, 1856–65.CrossRefGoogle ScholarPubMed
Mol, J.A., Garderen, E., Rutteman, G.R. & Rijnberk, A. (1996). New insights into the molecular mechanism of progestin-induced proliferation of mammary epithelium: induction of the local biosynthesis of growth hormone (GH) in the mammary gland of dogs, cats and humans. Journal of Steroid Biochemistry and Molecular Biology, 57, 67–71.CrossRefGoogle ScholarPubMed
Monsky, W.L., Carreira, C.M., Tsuzuki, Y.et al. (2002). Role of host microenvironment in angiogenesis and microvascular functions in human breast cancer xenografts: mammary fat pad versus cranial tumors. Clinical Cancer Research, 8, 1008–13.Google ScholarPubMed
Mori, M., Tominaga, T. & Tamaoki, B. (1978). Steroid metabolism in the normal mammary gland and in the dimethylbenzthracene-induced mammary tumour of rats. Endocrinolog, 102, 1387–97.CrossRefGoogle ScholarPubMed
Mori, M. & Tamaoki, B. (1980). In vitro metabolism of progesterone in the mammary tumour and the normal mammary gland of GRS/A strain of mice and dependency of some steroid-metabolizing enzyme activities upon ovarian function. European Journal of Cancer, 16, 185–93.CrossRefGoogle ScholarPubMed
Musgrove, E.A. & Sutherland, R.L. (1994). Cell cycle control by steroid hormones. Seminars in Cancer Biology, 5, 381–9.Google ScholarPubMed
Muti, P., Trevisan, M., Micheli, A.et al. (1996). Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period. Cancer Epidemiology, Biomarkers and Prevention, 5, 917–22.Google Scholar
Nandi, S., Guzman, R.C. & Yang, J. (1995). Hormones and mammary carcinogenesis in mice, rats, and humans: a unifying hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 92, 3650–7.CrossRefGoogle ScholarPubMed
Paris, A., Andre, F., Antignac, J.-P.et al. (2006). Hormones et promoteurs de croissance en productions animales: de la physiologie à l'évaluation du risque. INRA Productions Animales, 19, 149–240.Google Scholar
Pawlak, K.J. & Wiebe, J.P. (2007). Regulation of estrogen receptor (ER) levels in MCF-7 cells by progesterone metabolites. Journal of Steroid Biochemistry Molecular Biology, 107, 172–9.CrossRefGoogle ScholarPubMed
Pawlak, K.J., Zhang, G. & Wiebe, J.P. (2005). Membrane 5α-pregnane-3,20-dione (5αP) receptors in MCF-7 and MCF-10A breast cancer cells are up-regulated by estradiol and 5αP and down-regulated by the progesterone metabolites, 3α-dihydroprogesterone and 20α-dihydroprogesterone, with associated changes in cell proliferation and detachment. Journal of Steroid Biochemistry and Molecular Biology, 97, 278–88.CrossRefGoogle ScholarPubMed
Perry, G.A., Welshons, W.V., Bott, R.C. & Smith, M.F. (2005). Basis of melengestrol acetate action as a progestin. Domestic Animal Endocrinology, 28, 147–61.CrossRefGoogle ScholarPubMed
Pike, M.C., Spicer, D.V., Dahmoush, L. & Press, M.F. (1993). Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiologic Reviews, 15, 17–35.CrossRefGoogle ScholarPubMed
Pinheiro, S.P, Holmes, M.D., Pollak, M.N., Barbieri, R.L. & Hankinson, S.E. (2005). Racial differences in premenopausal endogenous hormones. Cancer Epidemiology, Biomarkers and Prevention, 14, 2147–53.CrossRefGoogle ScholarPubMed
Porch, J.V., Lee, I.M., Cook, N.R., Rexrode, K.M. & Buring, J.E. 2002. Oestrogen–progestin replacement therapy and breast cancer risk: the Women's Health Study (United States). Cancer Causes and Control, 13, 847–54.CrossRefGoogle Scholar
Potten, C.S., Watson, R.J., Williams, G.T.et al. (1988). The effect of age and menstrual cycle upon proliferative activity of the normal human breast. British Journal of Cancer, 58, 163–70.CrossRefGoogle ScholarPubMed
Prall, O.W., Sarcevic, B., Musgrove, E.A., Watts, C.K. & Sutherland, R.L. (1997). Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. The Journal of Biological Chemistry, 272, 10882–94.CrossRefGoogle ScholarPubMed
Radinsky, R. & Ellis, L.M. (1996). Molecular determinants in the biology of liver metastasis. Surgical Oncology Clinics of North America, 5, 215–29.Google ScholarPubMed
Raz, A. (1988). Adhesive properties of metastasizing tumor cells. Ciba Foundation Symposia, 141, 109–22.Google Scholar
Rossouw, J.E., Anderson, G.L., Prentice, R.L.et al. (2002). Risks and benefits of oestrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. Journal of the American Medical Association, 288, 321–33.Google ScholarPubMed
Sadano, H., Inoue, M. & Taniguchi, S. (1992). Differential expression of vinculin between weakly and highly metastatic B16-melanoma cell lines. Japanese Journal of Cancer Research, 83, 625–30.CrossRefGoogle ScholarPubMed
Santen, R.J., Manni, H., Harvey, H. & Redmond, C. (1990). Endocrine treatment of breast cancer in women. Endocrine Reviews, 11, 221–65.CrossRefGoogle ScholarPubMed
Schneider, B.P. & Miller, K.D. (2005). Angiogenesis of breast cancer. Journal of Clinical Oncology, 23, 1782–90.CrossRefGoogle ScholarPubMed
Segaloff, A. (1975). Steroids and carcinogenesis. Journal of Steroid Biochemistry, 6, 171–5.CrossRefGoogle ScholarPubMed
Sitruk-Ware, R. (2004). Pharmacological profile of progestins. Maturitas, 47, 277–83.CrossRefGoogle ScholarPubMed
Soto, A.M., Murai, J.T., Siiteri, P.K. & Sonnenschein, C. (1986). Control of cell proliferation: evidence for negative control on estrogen-sensitive T47D human breast cancer cells. Cancer Research, 46, 2271–5.Google ScholarPubMed
Soule, H.D., Maloney, T.M.et al. (1990). Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Research, 50, 6075–86.Google ScholarPubMed
Stahlberg, C., Pederson, A.T., Lynge, E. & Ottesen, B. (2003). Hormone replacement therapy and risk of breast cancer: the role of progestins. Acta Obstetrica et Gynecologica Scandinavica, 82, 335–44.CrossRefGoogle ScholarPubMed
Steeg, P.S. (2006). Tumor metastasis: mechanistic insights and clinical challenges. Nature Medicine, 12, 895–904.CrossRefGoogle ScholarPubMed
Sturgeon, S.R., Potischman, N., Malone, K.E.et al. (2004). Serum levels of sex hormones and breast cancer risk in premenopausal women: a case-control study (USA). Cancer Causes and Control, 15, 45–53.CrossRefGoogle Scholar
Sutherland, R.M. (1988). Cell and environment interactions in tumor microregions: the multicell spheroid model. Science, 240, 177–84.CrossRefGoogle ScholarPubMed
Suzuki, H., Nagata, H., Shimada, Y. & Konno, A. (1998). Decrease in gamma-actin expression, disruption of actin microfilaments and alterations in cell adhesion systems associated with acquisition of metastatic capacity in human salivary gland adenocarcinoma cell clones. International Journal of Oncology, 12, 1079–84.Google ScholarPubMed
Taguchi, S., Yoshida, S., Tanaka, Y. & Hori, S. (2001). Simple and rapid analysis of trenbolone and zeranol residues in cattle muscle and liver by stack-cartridge solidphase extraction and HPLC using on-line clean-up with EC and UV detection. Journal of the Food Hygienic Society of Japan, 42, 226–30.CrossRefGoogle Scholar
Thompson, C.B. (1995). Apoptosis in the pathogenesis and treatment of disease. Science, 267, 1456–62.CrossRefGoogle Scholar
Tiemann, U., Tomek, W., Schneider, F. & Vanselow, J. (2003). Effects of the mycotoxins α- and β-zearalenol on regulation of progesterone synthesis in cultured cells from porcine ovaries. Reproductive Toxicology, 17, 673–81.CrossRefGoogle ScholarPubMed
Topper, Y.J. & Freeman, C.S. (1980). Multiple hormone interactions in the developmental biology of the mammary gland. Physiological Reviews, 60, 1049–106.CrossRefGoogle ScholarPubMed
Trédan, O., Galmarini, C.M., Patel, K. & Tannock, I.F. (2007). Drug resistance and the solid tumor microenvironment. Journal of the National Cancer Institute, 99, 1441–54.CrossRefGoogle ScholarPubMed
Tsai, C.F., Chang, M.H., Pan, J.Q. & Chou, S.S. (2004). A method for the detection of trenbolone in bovine muscle and liver. Journal of Food and Drug Analysis, 12, 353–7.Google Scholar
Welsh, C. W. (1982). Hormones and murine mammary tumorigenesis: an historical view. In Hormonal Regulation of Mammary Tumors, ed. Leung, B.S.. Montreal: Eden Press, pp. 1–29.Google Scholar
Wiebe, J.P. (2005). Role of progesterone metabolites in mammary cancer. In Mammary Development, Function and Cancer, Special Issue of The Journal of Dairy Research, 72, 51–7.CrossRefGoogle ScholarPubMed
Wiebe, J.P. (2006). Progesterone metabolites in breast cancer. Endocrine-Related Cancer, 13, 717–38.CrossRefGoogle ScholarPubMed
Wiebe, J.P., Beausoleil, M., Zhang, G. & Cialacu, V. (2010). Opposing actions of the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP) on mitosis, apoptosis, and expression of Bcl-2, Bax and p21 in human breast cell lines. Journal of Steroid Biochemistry and Molecular Biology, 118, 125–32.CrossRefGoogle ScholarPubMed
Wiebe, J.P., Souter, L. & Zhang, G. (2006). Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment. Journal of Steroid Biochemistry and Molecular Biology, 100, 129–40.CrossRefGoogle ScholarPubMed
Wiebe, J.P., Muzia, D., Hu, J., Szwajcer, D.et al. (2000). The 4-pregnene and 5α-pregnane progesterone metabolites formed in nontumorous and tumorous breast tissue have opposite effects on breast cell proliferation and adhesion. Cancer Research, 50, 936–43.Google Scholar
Weiler, P.J. & Wiebe, J.P. (2000). Plasma membrane receptors for the cancer-regulating progesterone metabolites, 5α-pregnane-3, 20-dione (5αP) and 3α-hydroxy-4-pregnen-20-one (3αHP) in MCF-7 breast cancer cells. Biochemical and Biophysical Research Communications, 272, 731–7.CrossRefGoogle Scholar
Wiebe, J.P. & Muzia, D. (2001). The endogenous progesterone metabolite, 5α-pregnene-3,20-dione, decreases cell-substrate attachment, adhesion plaques, vinculin expression, and polymerized F-actin in MCF-7 breast cancer cells. Endocrine, 16, 7–14.CrossRefGoogle ScholarPubMed
Wiebe, J.P. & Lewis, M.J. (2003). Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydroxysteroid oxidoreductase and 3α(β)-hydroxysteroid oxidoreductases in tumorigenic (MCF-7, MDA-MB-231, T-47D) and nontumorigenic (MCF-10A) breast cell lines. BMC Cancer, 3, 9.CrossRefGoogle Scholar
Wiebe, J.P., Lewis, M.J., Cialacu, V., Pawlak, K.J.et al. (2005). The role of progesterone metabolites in breast cancer: Potential for new diagnostics and therapeutics. Journal of Steroid Biochemistry and Molecular Biology, 93, 201–8.CrossRefGoogle ScholarPubMed
Wollenhaupt, K., Jonas, L., Tiemann, U. & Tomek, W. (2004). Influence of the mycotoxins α- and β-zearalenol (ZOL) on regulators of cap-dependent translation control in pig endometrial cells. Reproductive Toxicology, 19, 189–99.CrossRefGoogle ScholarPubMed
Woodhouse, E.C., Chuaqui, R.F. & Liotta, L.A. (1997). General mechanisms of metastasis. Cancer, 80, 1529–37.3.0.CO;2-F>CrossRefGoogle Scholar
Wysowski, D.K., Comstock, G.W., Helsing, K.J. & Lau, H.L. (1987). Sex hormone levels in serum in relation to the development of breast cancer. American Journal of Epidemiology, 125, 791–9.CrossRefGoogle ScholarPubMed
Yen, S. (1990). Clinical endocrinology of reproduction. In Hormones: From Molecules to Diseases, ed. Baulieu, E-E. & Kelly, P.A.. Paris: 1Hermann, pp. 454–62.Google Scholar
Yoshioka, N., Akiyama, Y. & Takeda, N. (2000). Determination of alpha- and beta-trenbolone in bovine muscle and liver by liquid chromatography with fluorescence detection. Journal of Chromatography, B 739, 363–7.CrossRefGoogle ScholarPubMed
Yu, H., Shu, X.O., Shi, R., Dai, Q.et al. (2003). Plasma sex steroid hormones and breast cancer risk in Chinese women. International Journal of Cancer, 105, 92–7.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×