17beta-estradiol modulates UVB-induced cellular responses in estrogen receptors positive human breast cancer cells.
Genotoxic agents produce numerous cellular responses that are principally dedicated to maintain or restore DNA integrity. In human cells, nucleotide excision repair (NER) is one of the major pathways for the repair of DNA damage such as ultraviolet (UV) radiation-induced lesions. Endocrine disrupting compounds are environmental contaminants that interfere with the function of the endocrine system. Among them, the natural estrogen 17beta-estradiol (E(2)) exhibits the most potent activity. Some proteins directly or indirectly involved in NER also fulfill other functions such as transcription, DNA damage checkpoints or cell cycle. Moreover, steroids such as E(2) are believed to interact with a large number of proteins including some involved in NER and DNA damage checkpoint control. We therefore investigated the potential modulation of genotoxic stress-cells responses by E(2) treatment. Estrogen receptor (ER)-positive human breast cancer cells were submitted to E(2) before and/or after UVB irradiation and thereafter the repair kinetics of UV-induced DNA damage were evaluated. We report here that the repair rate of UVB-induced DNA damage is enhanced when cells are submitted to an estrogenic stimulation. Moreover, our results suggest that this response could be mediated by cell cycle regulatory proteins in a p53-independent manner.
Boulay
F
F
Laboratoire Santé Publique-Environnement, EA 3542, Université Paris Sud 11 - Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
Perdiz
D
D
D001943:Breast Neoplasms / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D016158:Genes, p53 / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D009376:Neoplasms, Hormone-Dependent; D011960:Receptors, Estrogen / Q000378:metabolism* / Q000528:radiation effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D011960:Receptors, Estrogen; D004958:Estradiol