Role of the human ERCC-1 gene in gene-specific repair of cisplatin-induced DNA damage

Larminat, Florence; Bohr, Vilhelm A.

doi:10.1093/nar/22.15.3005

Cited by 54 publications

(28 citation statements)

References 34 publications

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“…The molecular mechanisms of mammalian ICL repair are still unknown, but they are probably similar to those of S. cerevisiae and E. coli ICL repair. Incision of the ICLs is supposed to be performed by some of the NER proteins, as mutations in ERCC1 result in a decrease in the incision of ICLs and reduced repair-associated replication (35). In contrast to the situation in S. cerevisiae, where no significant differences among NER mutants are found, most mammalian NER-deficient cells are only moderately sensitive to ICL agents (11).…”

Section: Discussionmentioning

confidence: 99%

Disruption of Mouse SNM1 Causes Increased Sensitivity to the DNA Interstrand Cross-Linking Agent Mitomycin C

Dronkert

Wit

Boeve

et al. 2000

Molecular and Cellular Biology

118

110

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DNA interstrand cross-links (ICLs) represent lethal DNA damage, because they block transcription, replication, and segregation of DNA. Because of their genotoxicity, agents inducing ICLs are often used in antitumor therapy. The repair of ICLs is complex and involves proteins belonging to nucleotide excision, recombination, and translesion DNA repair pathways in Escherichia coli, Saccharomyces cerevisiae, and mammals. We cloned and analyzed mammalian homologs of the S. cerevisiae gene SNM1 (PSO2), which is specifically involved in ICL repair. Human Snm1, a nuclear protein, was ubiquitously expressed at a very low level. We generated mouse SNM1 ؊/؊ embryonic stem cells and showed that these cells were sensitive to mitomycin C. In contrast to S. cerevisiae snm1 mutants, they were not significantly sensitive to other ICL agents, probably due to redundancy in mammalian ICL repair and the existence of other SNM1 homologs. The sensitivity to mitomycin C was complemented by transfection of the human SNM1 cDNA and by targeting of a genomic cDNA-murine SNM1 fusion construct to the disrupted locus. We also generated mice deficient for murine SNM1. They were viable and fertile and showed no major abnormalities. However, they were sensitive to mitomycin C. The ICL sensitivity of the mammalian SNM1 mutant suggests that SNM1 function and, by implication, ICL repair are at least partially conserved between S. cerevisiae and mammals.

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Section: Discussionmentioning

confidence: 99%

Disruption of Mouse SNM1 Causes Increased Sensitivity to the DNA Interstrand Cross-Linking Agent Mitomycin C

Dronkert

Wit

Boeve

et al. 2000

Molecular and Cellular Biology

118

110

View full text Add to dashboard Cite

show abstract

“…Numerous mechanisms of cisplatin resistance have been identified, including decreasing drug uptake (e.g., by down-regulation of the copper transporter CTR1), increased efflux, and increased glutathione-based detoxification (6,9). In addition, resistance can also arise from changes that increase a cell's capacity to either repair or tolerate DNA damage (10)(11)(12). It is this latter group of DNA repair and tolerancebased mechanisms that have come under recent scrutiny as potential contributors to clinical cisplatin resistance.…”

mentioning

confidence: 99%

Suppression of Rev3, the catalytic subunit of Polζ, sensitizes drug-resistant lung tumors to chemotherapy

Doles¹,

Oliver²,

Cameron³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

164

148

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Platinum-based chemotherapeutic drugs are front-line therapies for the treatment of non-small cell lung cancer. However, intrinsic drug resistance limits the clinical efficacy of these agents. Recent evidence suggests that loss of the translesion polymerase, Polζ, can sensitize tumor cell lines to cisplatin, although the relevance of these findings to the treatment of chemoresistant tumors in vivo has remained unclear. Here, we describe a tumor transplantation approach that enables the rapid introduction of defined genetic lesions into a preclinical model of lung adenocarcinoma. Using this approach, we examined the effect of impaired translesion DNA synthesis on cisplatin response in aggressive late-stage lung cancers. In the presence of reduced levels of Rev3, an essential component of Polζ, tumors exhibited pronounced sensitivity to cisplatin, leading to a significant extension in overall survival of treated recipient mice. Additionally, treated Rev3-deficient cells exhibited reduced cisplatin-induced mutation, a process that has been implicated in the induction of secondary malignancies following chemotherapy. Taken together, our data illustrate the potential of Rev3 inhibition as an adjuvant therapy for the treatment of chemoresistant malignancies, and highlight the utility of rapid transplantation methodologies for evaluating mechanisms of chemotherapeutic resistance in preclinical settings.

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“…The excision repair cross-complementing (ERCC) gene family prevents damage to DNA caused by agents such as cisplatin (8) and low expression of ERCC1 correlates with response to this drug (9,10). Furthermore, an association between the expression of the HER-2 receptor and resistance to several anticancer drugs, including taxanes, cisplatin, and 5-FU, has been described (11), although the role of HER-2 in drug sensitivity is still uncertain.…”

mentioning

confidence: 99%

Association of Pretherapeutic Expression of Chemotherapy-Related Genes with Response to Neoadjuvant Chemotherapy in Barrett Carcinoma

Langer¹,

Specht²,

Becker³

et al. 2005

Clinical Cancer Research

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Purpose: We analyzed pretherapeutic gene expression patterns of patients with locally advanced adenocarcinomas of the esophagus with regard to response to neoadjuvant chemotherapy. Experimental Design: Pretherapeutic, paraffin-embedded, formalin-fixed endoscopic esophageal tumor biopsies of 38 patients with locally advanced esophageal adenocarcinomas (Barrett adenocarcinoma) were included. All patients underwent two cycles of cisplatin and 5-fluorouracil (5-FU) therapy with or without additional paclitaxel followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU metabolism-associated genes thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, MAP7, and ELF3, of platinum-and taxane-related genes caldesmon, ERCC1, ERCC4, HER-2/neu, and GADD45, and of multidrug resistance gene MRP1 were determined using real-time reverse transcriptase-PCR. Expression levels were correlated with response to chemotherapy, histopathologically assessed in surgically resected specimens. Results: Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (P = 0.012), caldesmon (P = 0.016), and MRP1 (P = 0.007). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (P = 0.013 and P = 0.015, respectively). Additionally, investigation of intratumoral heterogeneity of gene expression of relevant genes (MTHFR, caldesmon, HER-2/neu, ERCC4, and MRP1), verified in nine untreated Barrett adenocarcinomas by examination of five distinct tumor areas, revealed no significant heterogeneity in gene expression indicating that expression profiles obtained from biopsy material may yield a representative genetic expression profile of total tumor tissue. Conclusions: Our results indicate that determination of mRNA levels of few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced Barrett adenocarcinoma.

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Role of the human ERCC-1 gene in gene-specific repair of cisplatin-induced DNA damage

Abstract: ABSTRACT

Cited by 54 publications

References 34 publications

Disruption of Mouse SNM1 Causes Increased Sensitivity to the DNA Interstrand Cross-Linking Agent Mitomycin C

Disruption of Mouse SNM1 Causes Increased Sensitivity to the DNA Interstrand Cross-Linking Agent Mitomycin C

Suppression of Rev3, the catalytic subunit of Polζ, sensitizes drug-resistant lung tumors to chemotherapy

Association of Pretherapeutic Expression of Chemotherapy-Related Genes with Response to Neoadjuvant Chemotherapy in Barrett Carcinoma

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