This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xie, J. Articles by Haslam, S. Z. Search for Related Content PubMed PubMed Citation Articles by Xie, J. Articles by Haslam, S. Z. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL

Extracellular Matrix Regulates Ovarian Hormone-Dependent Proliferation of Mouse Mammary Epithelial Cells¹

Department of Physiology, Michigan State University, East Lansing, Michigan 48824

Address all correspondence and requests for reprints to: Sandra Z. Haslam, Department of Physiology, Michigan State University, East Lansing, Michigan 48824.

Mammary stromal cells can modulate steroid hormone responsiveness both in vivo and in vitro. One of the mechanisms by which stromal cells can influence epithelial cell behavior is by modifying the composition of the extracellular matrix (ECM). In this report, we have investigated the effects of five ECM molecules on control of epithelial cell proliferation by estrogen (E₂) and progestin (R5020) under serum-free culture conditions. To assess the contribution of mammary gland differentiation in determining epithelial cell interactions with ECM, the behavior of mammary epithelial cells derived from nulliparous and pregnant mice was compared.

We report the novel finding that the proliferative responses of mammary epithelial cells to progestin is influenced by specific ECM molecules. However, the primary determinant of hormonal responsiveness is the developmental state of the gland from which the epithelial cells were derived. Nulliparous-derived epithelial cells, proliferated in response to R5020 only on fibronectin (FN) and collagen IV (Col IV). The more highly differentiated, pregnancy-derived epithelial cells were not responsive to E₂ or R5020 on any ECM. To determine if steroid hormone receptors were targets of ECM-mediated effects, ER and PR levels were analyzed. In both nulliparous and pregnancy-derived cultures, PR binding levels were maintained at similar levels on all ECMs. However, ER levels were not maintained in nulliparous-derived cultures, and this may have contributed to the lack of a significant response to E₂. Alternatively or in addition, E₂-induced responses may require additional signals or growth factors that are provided by stromal cells in vivo or by serum supplementation in vitro.

These results demonstrate the ECM molecules, fibronectin and collagen IV, can modulate responsiveness of mammary epithelial cells to R5020 in vitro, and may be the mediators of stromal influences on hormone responsiveness in vivo. However, the specific effects of ECM and hormones are also determined by the developmental state of the mammary gland from which the cells are derived. Thus, mammary gland differentiation, ovarian hormones, and ECM composition may act in concert to determine the outcome of hormone treatment on cell proliferation.

This article has been cited by other articles:

				K. Roarty and R. Serra Wnt5a is required for proper mammary gland development and TGF-{beta}-mediated inhibition of ductal growth Development, November 1, 2007; 134(21): 3929 - 3939. [Abstract] [Full Text] [PDF]

				V. Novaro, C. D. Roskelley, and M. J. Bissell Collagen-IV and laminin-1 regulate estrogen receptor {alpha} expression and function in mouse mammary epithelial cells J. Cell Sci., July 15, 2003; 116(14): 2975 - 2986. [Abstract] [Full Text] [PDF]

				H.-Z. Zhang, J. M. Bennett, K. T. Smith, N. Sunil, and S. Z. Haslam Estrogen Mediates Mammary Epithelial Cell Proliferation in Serum-Free Culture Indirectly via Mammary Stroma-Derived Hepatocyte Growth Factor Endocrinology, September 1, 2002; 143(9): 3427 - 3434. [Abstract] [Full Text] [PDF]

				N. Sunil, J. M. Bennett, and S. Z. Haslam Hepatocyte Growth Factor Is Required for Progestin-Induced Epithelial Cell Proliferation and Alveolar-Like Morphogenesis in Serum-Free Culture of Normal Mammary Epithelial Cells Endocrinology, August 1, 2002; 143(8): 2953 - 2960. [Abstract] [Full Text] [PDF]

				T. L. Woodward, A. S. Mienaltowski, R. R. Modi, J. M. Bennett, and S. Z. Haslam Fibronectin and the {{alpha}}5{beta}1 Integrin Are Under Developmental and Ovarian Steroid Regulation in the Normal Mouse Mammary Gland Endocrinology, July 1, 2001; 142(7): 3214 - 3222. [Abstract] [Full Text] [PDF]

				T. L. Woodward, J. Xie, J. L. Fendrick, and S. Z. Haslam Proliferation of Mouse Mammary Epithelial Cells in Vitro: Interactions among Epidermal Growth Factor, Insulin-Like Growth Factor I, Ovarian Hormones, and Extracellular Matrix Proteins Endocrinology, October 1, 2000; 141(10): 3578 - 3586. [Abstract] [Full Text] [PDF]

				T. L. Woodward, H. Lu, and S. Z. Haslam Laminin Inhibits Estrogen Action in Human Breast Cancer Cells Endocrinology, August 1, 2000; 141(8): 2814 - 2821. [Abstract] [Full Text] [PDF]

				D. L. Buchanan, T. Kurita, J. A. Taylor, D. B. Lubahn, G. R. Cunha, and P. S. Cooke Role of Stromal and Epithelial Estrogen Receptors in Vaginal Epithelial Proliferation, Stratification, and Cornification Endocrinology, October 1, 1998; 139(10): 4345 - 4352. [Abstract] [Full Text] [PDF]