ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells.
Cisplatin is a valuable adjuvant to radiotherapy for the treatment of cervical cancer. Because the advantage of combining cisplatin with radiotherapy is likely to be attributable to additive cell killing by these 2 agents, such protocols should primarily benefit patients who have inherently cisplatin-sensitive tumors. Development of a molecular assay to rapidly evaluate the cisplatin responsiveness of cervical tumors would thus be extremely valuable. We investigated whether high pre-treatment mRNA levels of the ERCC1 nucleotide excision repair gene are predictive of cisplatin resistance in early-passage human cervical cancer cells, as they are in several other tumor types. Expression of the ERCC1 gene at the mRNA and protein levels was established by Northern and Western blotting, respectively, in a panel of single-cell-derived cervical carcinoma cell lines that exhibited a wide range of inherent sensitivity to cisplatin. There was a significant (p </= 0.011) correlation between ERCC1 mRNA levels and cisplatin resistance in these cell lines. However, there was no obvious relationship between ERCC1 protein levels and cisplatin resistance. Thus, the association between high ERCC1 mRNA levels and cisplatin resistance might be an epiphenomenon. Nonetheless, pre-treatment ERCC1 mRNA levels may be a useful molecular marker for identifying cervical tumors likely to be refractory to cisplatin, and further investigation in clinical biopsy material is warranted.
Britten
R A
RA
Division of Experimental Oncology, Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
Liu
D
D
Tessier
A
A
Hutchison
M J
MJ
Murray
D
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases; D005260:Female; D006801:Humans; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin