Functional screen of the fanconi anemia pathway in cancer cells by Fancd2 immunoblot.
The Fanconi genes BRCA2, FANCC and FANCG are mutated in a subset of pancreatic cancer. Additionally, the Fanconi pathway is inactivated, probably by FANCF promoter methylation, in a subset of ovarian cancers. The competence of the proximal Fanconi pathway was screened by an assay of Fancd2 monoubiquitination in a panel of 35 cancer cell lines: 15 breast, 6 prostate, 8 head and neck, 4 biliary cancers, an astrocytoma and a large cell lung carcinoma. Two (6%) cell lines displayed abnormal Fancd2 monoubiquitination: the head and neck cancer cell line FaDu and the breast cancer cell line UACC812. In UACC812, we found that FANCF was not expressed. In the case of FaDu, no explanation for the abnormal Fancd2 monoubiquitination was found. FaDu had a moderately increased sensitivity to mitomycin C, as compared to two Fanconi proficient head and neck cancer cell lines. Future studies should aim to investigate the involvement of defects in the Fanconi pathway in breast and head and neck cancer.
Van Der Heijden
Michiel S
MS
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Brody
Jonathan R
JR
Kern
Scott E
SE
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D052236:Fanconi Anemia Complementation Group D2 Protein; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects; D025801:Ubiquitin / Q000378:metabolism
C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins; D025801:Ubiquitin; D016685:Mitomycin