Characterization of the stimulatory effect of medroxyprogesterone acetate and chlormadinone acetate on growth factor treated normal human breast epithelial cells

Krämer, Elizabeth; Seeger, Harald; Krämer, B.; Wallwiener, D.; Mueck, Alfred O.

doi:10.1016/j.jsbmb.2005.11.002

Cited by 12 publications

(8 citation statements)

References 12 publications

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“…However, some evidence has emerged showing that PR-negative MCF10A cells are also directly responsive to progesterone [20], [33], [34], suggesting that progesterone action in the normal breast might also target PR-negative epithelial cells. For this reason, we investigated whether progesterone could influence the proportion of CSCs in irradiated MCF10A cells.…”

Section: Discussionmentioning

confidence: 99%

Generation of Breast Cancer Stem Cells by Steroid Hormones in Irradiated Human Mammary Cell Lines

Varès¹,

Chen²,

Wang³

et al. 2013

PLoS ONE

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Exposure to ionizing radiation was shown to result in an increased risk of breast cancer. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs). In order to assess whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured by flow cytometry the proportion of CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR)-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the downregulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant tumor-initiating CSCs.

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Section: Discussionmentioning

confidence: 99%

Generation of Breast Cancer Stem Cells by Steroid Hormones in Irradiated Human Mammary Cell Lines

Varès¹,

Chen²,

Wang³

et al. 2013

PLoS ONE

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“…10 Growth arrest was accompanied by decreased expression of both cyclin D1 and cyclin E, and increasing availability of p27. 10 On the other hand, it is known that progestins can also stimulate cell proliferation in mammary cells 25,30,32,35 and that various progestins can exert different effects. 36,37 We used the synthetic progestin MPA, which is commonly used in HT formulations.…”

Section: Discussionmentioning

confidence: 99%

Effects of estradiol and medroxyprogesterone acetate on expression of the cell cycle proteins cyclin D1, p21 and p27 in cultured human breast tissues

Eigėlienė¹,

Härkönen²,

Erkkola³

2008

Cell Cycle

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“…This supposition is supported by the lack of progesteroneinduced proliferation of breast explants in nude mice (5), of immortalized breast epithelial cells lacking nuclear PR expression (25), and in breast cancer cell lines lacking nuclear PR (40). In contrast to these observations, recent studies with the immortalized nuclear PR-negative breast epithelial cell line, MCF-10A, show a progestin-induced growth response when combined with tyrosine kinase growth factors (24,25). Because proliferation is a complex action requiring activation of many cellular pathways, we hypothesized that progesterone/ progestin may have metabolic effects via nongenomic regulation.…”

mentioning

confidence: 81%

“…Recently, a synergistic increase in proliferation by a progestin in combination with a tyrosine kinase growth factor was demonstrated in MCF-10A cells (24,25). The explanation for this observation may involve the progestin-induced enhanced cellular respiration discussed above.…”

mentioning

confidence: 98%

Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells

Behera

Dai

Garde

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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As an example, progesterone levels correlate with increased epithelial cell proliferation, but there is discordance between the dividing cells and the cells with nuclear progesterone receptor expression. The release of paracrine growth factors from nuclear receptor-positive cells has been postulated as a mechanism, since in vitro studies show a lack of growth effect by progesterone in breast epithelial cells lacking nuclear receptors. This study examined possible nongenomic effects of progesterone in breast epithelia by using MCF-10A cells known to lack nuclear progesterone receptor expression. Treatment for 30 -60 min with progesterone or the progestin, R5020, increased mitochondrial activity as shown by an increase in mitochondrial membrane potential (hyperpolarization) with a concordant increase in total cellular ATP. The reaction was inhibited by a specific progesterone receptor antagonist and not affected by the translation inhibitor cycloheximide. Progestin treatment inhibited apoptosis induced by activation of the FasL pathway, as shown by a decrease in sub-G 1 cell fraction during fluorescence-activated cell sorting and a decrease in caspase 3/7 levels. Progestin treatment did not alter the cell cycle over 48 h. Our study demonstrates a nongenomic action of progesterone on benign breast epithelial cells, resulting in enhanced cellular respiration and protection from apoptosis.progesterone; MCF-10A cells; mitochondria; apoptosis; cellular respiration PREVIOUS STUDIES HAVE SHOWN a discordance between the proliferative action of progesterone in the breast and the content of nuclear progesterone receptors (PR-B and PR-A) in breast epithelial cells. As examples, the mitotic rate of breast epithelial cells is greatest in the progesterone-dominant luteal phase (44). Exogenous administration of estrogen plus progestin results in greater breast epithelial proliferation than estrogen alone (15, 18). The progesterone receptor knockout (PRKO) mouse, an excellent model for the function of nuclear PR in mammary gland development, supports a proliferative role. PR-B is primarily responsible for gland development, with PRKO-B mice showing less extensive ductal development and lack of alveolar terminal end buds (7,29). In contrast to these physiological effects, very few breast epithelial cells appear to express nuclear PR. In immunocytochemical studies of human breast tissue, from 6 to 13% of ductal epithelial cells express PR (6, 37), with the two PR isoforms, B and A, typically localizing in the same cell (14). Immunocytochemical analysis of proliferation by detection of Ki67 antigen in human breast or autoradiographs of [ 3 H]thymidine incorporation in rodent mammary samples show nuclear PR-expressing cells to be nonproliferating. Adjacent cells lacking nuclear PR expression have greater mitotic activity (23). This disassociation between nuclear PR expression and proliferation led to the hypothesis that nuclear PR-expressing cells regulate proliferation of adjacent cells via the control of paracrine factors (4).This ...

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Characterization of the stimulatory effect of medroxyprogesterone acetate and chlormadinone acetate on growth factor treated normal human breast epithelial cells

Cited by 12 publications

References 12 publications

Generation of Breast Cancer Stem Cells by Steroid Hormones in Irradiated Human Mammary Cell Lines

Generation of Breast Cancer Stem Cells by Steroid Hormones in Irradiated Human Mammary Cell Lines

Effects of estradiol and medroxyprogesterone acetate on expression of the cell cycle proteins cyclin D1, p21 and p27 in cultured human breast tissues

Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells

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