Excision repair cross complementing-group 1: gene expression and platinum resistance.
Platinum compounds induce their cytotoxic effect by binding to a DNA molecule in the form of a platinum-DNA-adduct. Many previous studies have shown that the level of platinum-DNA-adduct correlats with response to platinum-based chemotherapy. Although the mechanism of platinum resistance in vivo is not clearly understood, laboratory studies on cancer cell lines suggest that nucleotide excision repair (NER) is the main mechanism responsible for this resistance by increased platinum-DNA-adduct removal. NER pathway is a network of many proteins gathered in a DNA-repair system. The excision repair cross complementing-group 1 (ERCC1) gene has the leading role in NER-pathway because of its damage recognition and excision ability. In this report we reviewed the pathway leading to ERCC1 gene transcription and translation in cancer cells when exposed to cisplatin. We summarized data from different cancer cell lines and human cancers showing that the high level of ERCC1-mRNA and/or ERCC1 protein is associated with resistance to platinum compounds with direct impact on cancer patient survival and finally we analyzed drugs interfering with ERCC1 gene expression and causing the reversal of the platinum resistance when given to cancer cells prior to platinum-based chemotherapy.
Altaha
Ramin
R
Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506-2519, USA. raltaha@hsc.wvu.edu.
Liang
Xiaobing
X
Yu
Jing Jie
JJ
Reed
Eddie
E
D000818:Animals; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology*; D004720:Endonucleases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010984:Platinum / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D004268:DNA-Binding Proteins; D010984:Platinum; C071447:ERCC1 protein, human; D004720:Endonucleases