title: Genotoxic stress modulates CDC25C phosphatase alternative splicing in human breast cancer cell lines.
abstract: CDC25 (cell division cycle 25) phosphatases are essential for cell cycle control under normal conditions and in response to DNA damage. They are represented by three isoforms, CDC25A, B and C, each of them being submitted to an alternative splicing mechanism. Alternative splicing of many genes is affected in response to genotoxic stress, but the impact of such a stress on CDC25 splicing has never been investigated. In this study, we demonstrate that genotoxic agents (doxorubicin, camptothecin, etoposide and cisplatin), alter the balance between CDC25C splice variants in human breast cancer cell lines both at the mRNA and protein levels. This modulation occurs during the response to moderate, sub-lethal DNA damage. Our results also suggest that the CDC25C splice variants expression shift induced by a genotoxic stress is dependent on the ATM/ATR signaling but not on p53. This study highlights the modulation of CDC25C alternative splicing as an additional regulatory event involved in cellular response to DNA damage in breast cancer cells.
authors.affiliation: Université de Lorraine, LIMBP-SRSMC, Rue du Général Delestraint, EA 3940, Metz F-57070, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Albert
authors.forename: Eric
authors.initials: E
authors.lastname: Battaglia
authors.forename: Carolino
authors.initials: C
authors.lastname: Monteiro
authors.forename: Denyse
authors.initials: D
authors.lastname: Bagrel
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects*; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020687:cdc25 Phosphatases / Q000235:genetics*
chemical_list: D009153:Mutagens; D012333:RNA, Messenger; D004247:DNA; D020687:cdc25 Phosphatases