Progestins induce catalase activities in breast cancer cells through PRB isoform: correlation with cell growth inhibition.
Reactive oxygen species (ROS) have been suggested to participate in tumor emergence due to their mitogenic and apoptotic signaling, and as contributors to DNA structural damage. Here we report that progesterone and various synthetic steroids with progestin potencies (norethisterone acetate, MPA, and Tibolone) counteract cell growth induced by hydrogen peroxide (H(2)O(2)), through a potent induction of catalase activities, in breast cancer cells and normal human epithelial breast cells. At physiological concentrations, progesterone and the pure progestin, Org2058, displayed the most potent H(2)O(2) detoxification ability suggesting its effect was characteristic of its progestin potency. We also report on the enhancement of catalase activities by progesterone receptor isoform B (PRB), as determined from experiments using antiprogestins and MDA-MB-231, cells engineered for the selective expression of progesterone receptor isoform A or B. The potent action of progesterone on catalase activities indicates its contribution to a beneficial role in breast cell homeostasis.
Petit
Emile
E
INSERM-UPMC Univ Paris 06, UMRS 938, Hôpital Saint-Antoine, Paris, France.
Courtin
Aurélie
A
Kloosterboer
Helenius J
HJ
Rostène
William
W
Forgez
Patricia
P
Gompel
Anne
A
D001940:Breast / Q000166:cytology / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D009652:Norpregnenes / Q000378:metabolism / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D011374:Progesterone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011372:Progestins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D016877:Oxidants; D011372:Progestins; D017382:Reactive Oxygen Species; D011980:Receptors, Progesterone; C097314:progesterone receptor B; D011374:Progesterone; D006861:Hydrogen Peroxide; D002374:Catalase; C027385:tibolone