Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines.
Over 80% of patients with advanced metastatic testis tumors can be cured using cisplatin-based combination chemotherapy. This is unusual as metastatic cancer in adults is usually incurable. Cell lines derived from testis tumors retain sensitivity to cisplatin in vitro. We previously investigated 2 testis tumor cell lines with a low capacity to remove cisplatin-induced DNA damage and found that they had low levels of the DNA nucleotide excision repair proteins XPA, ERCC1 and XPF. To determine whether low levels of XPA, ERCC1 and XPF proteins are characteristic of testis tumor cell lines, we investigated 35 cell lines derived from cancers to determine whether groups of cell lines from diverse tissue origins differ from one another in constitutive levels of these NER proteins. Quantitative immunoblotting was used to compare groups of cell lines representing prostate, bladder, breast, lung, cervical, ovarian and testis cancers. Only the 6 testis tumor cell lines showed significantly lower mean levels of XPA (p = 0.001), XPF (p = 0.001) and ERCC1 (p = 0.004) proteins from the other groups. Our results encourage further investigation of the possibility that low levels of these nucleotide excision repair proteins could be related to the favorable response of testis tumors to cisplatin-based chemotherapy.
Welsh
Carey
C
University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213-1863, USA.
Day
Roger
R
McGurk
Claire
C
Masters
John R W
JR
Wood
Richard D
RD
Köberle
Beate
B
D045744:Cell Line, Tumor; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004720:Endonucleases / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D016018:Least-Squares Analysis; D008297:Male; D009362:Neoplasm Metastasis; D013736:Testicular Neoplasms / Q000188:drug therapy; D013737:Testis / Q000378:metabolism*; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C095888:xeroderma pigmentosum group F protein; C071447:ERCC1 protein, human; D004720:Endonucleases