Nucleotide Excision Repair Pathways Involved in Cisplatin Resistance in Non-Small-Cell Lung Cancer

Rosell, Rafael; Tarón, Miquel; Barnadas, Agustí; Scagliotti, Giorgio V.; Sarries, Carme; Roig, Bárbara

doi:10.1177/107327480301000404

Cited by 138 publications

(92 citation statements)

References 30 publications

(30 reference statements)

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“…ERCC1 overexpression in non-small lung tumours was related to cisplatin resistance and resistance decreased after antisense ERCC1 inhibition (Rosell et al, 2003). Ovarian cancer lines that developed resistance after exposure to cisplatin in vitro were found to have increased ERCC1 levels (Ferry et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance

Melton

2011

Oncogene

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The incidence of malignant melanoma is growing rapidly worldwide and there is still no effective therapy for metastatic disease. Melanoma is the second most common cancer among young adults in the UK, where incidence rates have more than quadrupled since the 1970s. Increased expression of a number of DNA repair genes has been reported in melanoma and this likely contributes to its extreme resistance to conventional DNA-damaging chemotherapeutics. One such chemotherapeutic that is effective against a range of other cancers, but not melanoma, is cisplatin. The DNA repair proteins ERCC1 and XPF are needed to remove cisplatin-induced DNA damage and we have investigated the response of these proteins to cisplatin in melanoma. The expression of both genes is induced by cisplatin. Use of a MEK inhibitor showed that ERCC1, but not XPF induction was regulated by the mitogen-activated protein kinase (MAPK) pathway, with reduction in expression of DUSP6, the phosphatase that inactivates the extracellular signal-regulated kinase (ERK), being particularly important. DUSP6 overexpression prevented cisplatin induction of both ERCC1 and XPF, resulting in increased sensitivity to cisplatin. A novel ERCC1 mRNA was found that initiated upstream of the normal transcription initiation site, and was strongly regulated by both cisplatin and the MAPK pathway and its role in cisplatin resistance merits further study. The cisplatin induction of ERCC1 and XPF provides important insights into the resistance of melanoma to DNA-damaging chemotherapeutics, which is one of the major obstacles to melanoma treatment.

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Section: Discussionmentioning

confidence: 99%

Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance

Melton

2011

Oncogene

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“…Excision repair cross complementation-1 plays a pivotal role in NER pathway, influencing the repair of platinum/ DNA damage because of its adducts recognition and excision ability (Lee et al, 1993). It has been indicated that subjects with lower ERCC-1 levels had lower DNA repair capacity (Rosell et al, 2003). On the other hand, XRCC-1 has been shown to be involved in the repair of other types of DNA damage caused by CDDP including double-stranded breaks (Weaver et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil

Chen

Tsou

et al. 2007

Br J Cancer

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To identify mechanisms underlying oxaliplatin resistance, a subline of the human gastric adenocarcinoma TSGH cell line, S3, was made resistant to oxaliplatin by continuous selection against increasing drug concentrations. Compared with the parental TSGH cells, the S3 subline showed 58-fold resistance to oxaliplatin; it also displayed 11-, 2-, and 4.7-fold resistance to cis-diammine-dichloroplatinum (II) (CDDP), copper sulphate, and arsenic trioxide, respectively. Interestingly, S3 cells were fourfold more susceptible to 5-fluorouracilinduced cytotoxicity due to downregulation of thymidylate synthase. Despite elevated glutathione levels in S3 cells, there was no alteration of resistant phenotype to oxaliplatin or CDDP when cells were co-treated with glutathione-depleting agent, l-buthionine-(S,R)-sulphoximine. Cellular CDDP and oxaliplatin accumulation was decreased in S3 cells. In addition, amounts of oxaliplatin-and CDDP -DNA adducts in S3 cells were about 15 and 40% of those seen with TSGH cells, respectively. Western blot analysis showed increased the expression level of copper transporter ATP7A in S3 cells compared with TSGH cells. Partial reversal of the resistance of S3 cells to oxaliplatin and CDDP was observed by treating cell with ATP7A-targeted siRNA oligonucleotides or P-type ATPaseinhibitor sodium orthovanadate. Besides, host reactivation assay revealed enhanced repair of oxaliplatin-or CDDP-damaged DNA in S3 cells compared with TSGH cells. Together, our results show that the mechanism responsible for oxaliplatin and CDDP resistance in S3 cells is the combination of increased DNA repair and overexpression of ATP7A. Downregulation of thymidylate synthase in S3 cells renders them more susceptible to 5-fluorouracil-induced cytotoxicity. These findings could pave ways for future efforts to overcome oxaliplatin resistance.

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“…In addition, there is NF-jB differentially affects DNA damage-induced apoptosis E Strozyk et al increasing evidence that UVA also can induce CPDs but certainly to a lesser degree than UVB (Besaratinia et al, 2005). Cisplatin induces bulky adducts, which like UVBinduced damage are also removed by the nucleotide excision repair (Rosell et al, 2003). In contrast, g-radiation, doxorubicin and etoposide primarily induce strand breaks.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

et al. 2006

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Nucleotide Excision Repair Pathways Involved in Cisplatin Resistance in Non-Small-Cell Lung Cancer

Abstract: The level of evidence for many assays is limited, and only ERCC1 mRNA levels have been analyzed extensively. The impact of ERCC1 should be fully validated in prospective clinical trials.

Cited by 138 publications

References 30 publications

Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance

Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance

Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

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