Nucleotide excision repair protein levels vis-à-vis anticancer drug resistance in 60 human tumor cell lines.
OBJECTIVE
Nucleotide excision repair (NER) is a multi-enzyme DNA repair system in eukaryotes. Several NER genes in this system including XPA, XPB, ERCC1, and ERCC2 (XPD) have been implicated in anticancer drug resistance in human tumor cells. This study was designed to investigate the relationship between the expression of NER protein and the drug-resistance of human tumor cell lines.


METHODS
In this study, The authors assessed the levels of the above mentioned proteins, by utilizing Western blot analysis, in the USA National Cancer Institute (NCI) panel of 60 human tumor cell lines and correlated to the cytotoxicity patterns of 170 compounds that constitute the standard agent (SA) database.


RESULTS
The ERCC1, XPB, and XPD protein expression patterns yielded significant negative Pearson correlations with 13, 17, and 32 out of the 170 compounds, respectively (P < 0.05). XPA produced a random assortment of negative and positive correlations and did not appear to confer an overall resistance or sensitivity to these drugs. Protein expression was also compared with a pre-defined categorisation of the standard agents into six mechanism-of-action (MOA) groups resulting in an inverse association between XPD and alkylating agent sensitivity.


CONCLUSIONS
Our present data demonstrate that XPD protein levels correlate with resistance to alkylating agents in human tumor cell lines, suggesting that XPD plays an important role in the development of this resistance.
Chen
Zhong-ping
ZP
Cancer Center, Sun Yat-sen University, Guangzhou 510060, P. R. China. chenzp@gzsums.edu.cn
Malapetsa
Areti
A
Monks
Anne
A
Myers
Timothy G
TG
Mohr
Gérard
G
Sausville
Edward A
EA
Scudiero
Dominic A
DA
Panasci
Lawrence C
LC
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D004265:DNA Helicases; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D004720:Endonucleases; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D051760:Xeroderma Pigmentosum Group A Protein; D051759:Xeroderma Pigmentosum Group D Protein
D018906:Antineoplastic Agents, Alkylating; D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C072022:XPBC-ERCC-3 protein; C071447:ERCC1 protein, human; D004720:Endonucleases; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human