Insulin-like Growth Factor Binding Protein (Igfbp)-5 is Upregulated During Both Differentiation and Apoptosis in Primary Cultures of Mouse Mammary Epithelial Cells.
From: Molecular Recognition Group, Hannah Research Institute, Ayr, Scotland.
Journal of cellular physiology
- Publish Date: May 2006
- ISSN: 0021-9541
- Volume: 207
- Issue: 2
- Pages: 471-9
- Medium: Print
- Language: English
- Citation (JAMA): Lochrie Jennifer D, Phillips Kirsten, Tonner Elizabeth, et al. Insulin-like Growth Factor Binding Protein (Igfbp)-5 is Upregulated During Both Differentiation and Apoptosis in Primary Cultures of Mouse Mammary Epithelial Cells.. J. Cell. Physiol. May 2006;207:471-9
Abstract
We have previously demonstrated that insulin-like growth factor binding protein-5 (IGFBP-5) is upregulated following treatment of the mouse mammary epithelial cell line HC11 with lactogenic hormones (dexamethasone, insulin, and prolactin-DIP). In addition, we have also shown that IGFBP-5 is upregulated in mammary epithelial cells in vivo during involution of the rodent mammary gland. We have, therefore, postulated that there may be a dual regulation of IGFBP-5 expression during the temporally separated processes of differentiation and apoptosis of mammary epithelial cells. To test this hypothesis further, we have used a phenotypically differentiated model, which comprises primary cultures of mouse mammary epithelial cells grown on a layer of EHS (Engelbreth-Holm-Swarm) extracellular matrix. We show that lactogenic hormone treatment (hydrocortisone, insulin, and prolactin-HIP) of these cultures induces the upregulation of IGFBP-5 thus replicating the results obtained with the HC11 cell line. In addition, following the induction of apoptosis in primary cultures of mammary epithelial cells by treatment with TGFbeta-3, IGFBP-5 expression is also upregulated. In parallel with this upregulation of IGFBP-5, there is also an increase in the levels of cleaved caspase-3, a well-characterized marker of cellular apoptosis. These findings confirm previous in vivo work demonstrating an increase in IGFBP-5 expression during involution of the mouse mammary gland. When HC11 cells are cultured under serum-free conditions (a well-characterized apoptotic insult in cell culture), there is also an increase in cleaved caspase-3 levels. Unexpectedly, in the presence of TGFbeta-3, caspase-3 levels are attenuated. In the presence of DIP, caspase-3 levels are also decreased in HC11 cells. As described previously, TGFbeta-3 inhibits beta-casein synthesis in HC11 cells. In the HC11 cell line (in contrast to primary cultures of mammary epithelial cells), there is no evidence for TGFbeta-3 induction of IGFBP-5 under either serum-free or DIP-supplemented conditions. We believe our data with primary cultures of mammary epithelial cells support the hypothesis of dual regulation of IGFBP-5 expression during both differentiation and apoptosis in the mammary gland and emphasizes the importance of using appropriate cell culture models to investigate such phenomena in this tissue. We discuss the possible implications of our observations in relation to the physiological processes of pregnancy, lactation, and involution in the mammary gland and the associated changes in mammary epithelial cell function.
Mesh Headings (Keywords): Animals, Apoptosis, Caseins, Caspase 3, Caspases, Cell Differentiation, Cell Line, Cells, Cultured, Culture Media, Serum-Free, Epithelial Cells, Female, Gene Expression, Hydrocortisone, Insulin, Insulin-Like Growth Factor Binding Protein 5, Mammary Glands, Animal, Mice, Pregnancy, Prolactin, Transforming Growth Factor beta, Transforming Growth Factor beta3, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16419030
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.