Open AccessGenotoxic stress modulates CDC25C phosphatase alternative splicing in human breast cancer cell lines
Author(s) -
Albert Hélène,
Battaglia Eric,
Monteiro Carolino,
Bagrel Denyse
Publication year - 2012
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2012.06.003
Subject(s) - cdc25a , dna damage , alternative splicing , biology , cdc25 , rna splicing , dna repair , cell cycle , chek1 , microbiology and biotechnology , cancer research , cell cycle checkpoint , gene isoform , genetics , gene , cyclin dependent kinase 1 , dna , rna
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.