Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells.
The effects of progesterone on breast epithelial cells remain poorly defined with observations showing both proliferative and antiproliferative effects. 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.
Behera
Millie A
MA
Duke Univ., Box 3928, DUMC, Durham, NC 27710, USA.
Dai
Qunsheng
Q
Garde
Rachana
R
Saner
Carrie
C
Jungheim
Emily
E
Price
Thomas M
TM
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000494:pharmacology; D007610:Kallikreins / Q000096:biosynthesis; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019014:fas Receptor / Q000502:physiology
D051798:Inhibitor of Differentiation Protein 1; D011500:Protein Synthesis Inhibitors; D011980:Receptors, Progesterone; D053773:Transforming Growth Factor beta1; D019014:fas Receptor; D011374:Progesterone; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D007610:Kallikreins; D020169:Caspases; D020782:Matrix Metalloproteinases
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