Functional analysis of familial Asp67Glu and Thr1051Ser BRCA1 mutations in breast/ovarian carcinogenesis.
Estrogen is believed to be pre-initiator in the risk of breast cancer. The BRCA1 is a tumor suppressor gene associated with breast and ovarian cancer risk. This report describes functional analysis of two BRCA1 missense mutations (Asp67Glu and Thr1051Ser) observed in the familial breast/ovarian cancer patients in Thailand. Levels of luciferase activity of the two mutations were relatively lower than in the wild-type BRCA1. It is indicated that mutants may fail to promote the estrogen receptor dependent functions. It is presumed that estrogen and insulin/IGF-1 regulate c-Myc and cyclin D1 during breast cancer cell proliferation. It is also likely to affect ubiquitination mechanism. Since three affected cancer families carry the Asp67Glu mutation, it is believed that this type of mutation could have some effect on breast/ovarian cancer progression.
Pongsavee
Malinee
M
Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Rangsit Campus, Pathumthani, Thailand.
Patmasiriwat
Pimpicha
P
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Salaya Campus, Nakornpathom, Thailand.
Saunders
Grady F
GF
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D045744:Cell Line, Tumor; D004967:Estrogens / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D011960:Receptors, Estrogen / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004967:Estrogens; D011960:Receptors, Estrogen