Progesterone prevents radiation-induced apoptosis in breast cancer cells.
Sex steroid hormones play an essential role in the control of homeostasis in the mammary gland. Although the involvement of progesterone in cellular proliferation and differentiation is well established, its exact role in the control of cell death still remains unclear. As dysregulation of the apoptotic process plays an important role in the pathogenesis of breast cancer, we investigated the regulation of apoptosis by progesterone in various breast cancer cell lines. Our results show that progesterone treatment protects against radiation-induced apoptosis. This prevention appears to be mediated by the progesterone receptor and is unrelated to p53 status. There is also no correlation with the intrinsic hormonal effect on cell proliferation, as the presence of cells in a particular phase of the cell cycle. Surprisingly, progesterone partly allows bypassing of the irradiation-induced growth arrest in G(2)/M in PgR+ cells, leading to an increase in cell proliferation after irradiation. One consequence of this effect is a higher rate of chromosome damage in these proliferating progesterone-treated cells compared to what is observed in untreated irradiated cells. We propose that progesterone, by inhibiting apoptosis and promoting the proliferation of cells with DNA damage, potentially facilitates the emergence of genetic mutations that may play a role in malignant transformation.
Vares
Guillaume
G
Laboratoire de Cancérologie Expérimentale, Département de Radiobiologie et Radiopathologie, Commissariat à l'Energie Atomique, 92265 Fontenay-aux-Roses, cedex, France.
Ory
Katherine
K
Lectard
Bruno
B
Levalois
Céline
C
Altmeyer-Morel
Sandrine
S
Chevillard
Sylvie
S
Lebeau
Jérôme
J
D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations; D004249:DNA Damage; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015162:Micronucleus Tests; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects
D006727:Hormone Antagonists; D011837:Radiation-Protective Agents; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D015735:Mifepristone; D011374:Progesterone