Progesterone prevents radiation-induced apoptosis in breast cancer cells

• Published in: Oncogene Vol. 23; no. 26; pp. 4603 - 4613
• Main Authors: VARES, Guillaume, ORY, Katherine, LECTARD, Bruno, LEVALOIS, Céline, ALTMEYER-MOREL, Sandrine, CHEVILLARD, Sylvie, LEBEAU, Jérome
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 03.06.2004; Nature Publishing Group
• Subjects: Ageing, cell death; Apoptosis; Apoptosis - genetics; Apoptosis - radiation effects; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Cell cycle; Cell Cycle - drug effects; Cell Cycle - radiation effects; Cell death; Cell Division - drug effects; Cell Division - radiation effects; Cell growth; Cell physiology; Cell proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosome Aberrations; Chromosomes; DNA Damage; Female; Fundamental and applied biological sciences. Psychology; Gamma Rays - adverse effects; Gene Expression Regulation - drug effects; Genetic transformation; Gynecology. Andrology. Obstetrics; Homeostasis; Hormone Antagonists - pharmacology; Humans; Mammary gland; Mammary gland diseases; Medical sciences; Micronucleus Tests; Mifepristone - pharmacology; Molecular and cellular biology; p53 Protein; Progesterone; Progesterone - pharmacology; Radiation; Radiation-Protective Agents - pharmacology; Receptors, Progesterone - drug effects; Receptors, Progesterone - genetics; Receptors, Progesterone - radiation effects; Steroid hormones; Tumor cell lines; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - drug effects; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - radiation effects; Tumors; Mammary gland diseases; Irradiation; Breast cancer; cancer; Mammary gland; Progesterone; Malignant tumor; Sex steroid hormone; Carcinogenesis; breast; Ovarian hormone; Apoptosis
• DOI: 10.1038/sj.onc.1207601
• ISSN: 0950-9232

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.