282. Anti-apoptotic effects of glucocorticoids and progesterone in a human mammary epithelial cell line
M. N. Berg A , B. J. Waddell A and A. M. Dharmarajan ASchool of Anatomy and Human Biology, The University of Western Australia, Crawley, WA, Australia
Reproduction, Fertility and Development 17(9) 118-118 https://doi.org/10.1071/SRB05Abs282
Submitted: 26 July 2005 Accepted: 26 July 2005 Published: 5 September 2005
Abstract
Previous studies in the lactating rat mammary gland have shown that removal of both progesterone and glucocorticoids can induce apoptosis, and that replacement with either steroid alone can prevent this effect.1 These results raised the possibility that progesterone may exert its anti-apoptotic effects in the mammary gland via the glucocorticoid receptor (GR). A similar mechanism has previously been proposed to account for the action of progesterone in the corpus luteum.2 To assess this possibility we examined the effects of glucocorticoids and progesterone on apoptosis in the non-tumorigenic human mammary epithelial cell line, MCF-10A.
Initial PCR analysis demonstrated that MCF-10A cells do not express progesterone receptor mRNA (PR-A or PR-B). MCF-10A cells were incubated in serum-free DMEM:F12 medium with additives in the presence or absence of cortisol (10–6M) or progesterone (10–5M to 10–8M). DNA fragmentation (an index of apoptosis) was quantitated by either 3′-end labelling or by a novel method of image analysis of SYBR® gold-stained gels. DNA fragmentation was clearly increased after 24 h in the absence of cortisol, consistent with previous reports for this cell line.3 In a separate experiment, replacement of cortisol with progesterone also reduced apoptosis by 48 h, although this protection was evident only at the two highest progesterone doses (10–5M and 10–6M).
These results suggest that despite the absence of a progesterone receptor, progesterone is able to prevent apoptosis in MCF-10A cells, albeit at a physiologically high doses. This supports the hypothesis that some actions of progesterone may be mediated via the GR. Further studies are required to determine the precise molecular pathways by which cortisol and progesterone prevent apoptosis.
(1) Berg MN et al. (2002) Endocrinology 143, 222–227.
(2) Sugino N et al. (1997) Endocrinology 138, 4497–4500.
(3) Moran TJ et al. (2000) Cancer Res 60, 867–872.
