Molecular pathways involved in response to ionizing radiation of ID-8 mouse ovarian cancer cells expressing exogenous full-length Brca1 or truncated Brca1 mutant.
BRCA1 germline mutations have been linked to the development of hereditary breast and ovarian cancers. Recent studies suggest that BRCA1 may function in the regulation of basic cellular processes, including gene transcription, and sensing and/or repair of DNA damage. To further delineate the BRCA1 upstream and downstream steps involved in its role in the cellular response to ionizing radiation, we compared the effects of expression of an exogenous full-length Brca1 with those of a truncated Brca1 mutant in the ID-8 mouse ovarian cancer cell line after irradiation. We found that expression of both full-length and truncated Brca1 increased resistance to ionizing radiation. Expression of truncated, but not full-length, Brca1 then allowed us to identify new potential downstream targets of mutated BRCA1 like MAPK/ERK pathway members and also key genes involved in mutated BRCA1 signaling pathway response to ionizing radiation such as p53 and p21WAF1/CIP1. We therefore established an in vitro mouse model for studying the molecular effects of human BRCA1 germline mutations.
Sylvain
V
V
Laboratoire d'Oncologie Moleculaire, Centre Jean Perrin, 58 Rue Montalembert, BP 392, 63 011 Clermont-Ferrand Cedex 1, France.
Lafarge
S
S
Bignon
Y J
YJ
D000818:Animals; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics*; D002453:Cell Cycle; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D019313:BRCA1 Protein; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D020929:Mitogen-Activated Protein Kinase Kinases