The authors investigated whether p38 MAPK activity contributed to the viability of cisplatin in lung cancer cell lines from never or light smokers and to ERCC1 mRNA expression.
Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity.
Collectively, these data suggest that there is a synergistic relationship between PARP inhibition and low ERCC1 expression in NSCLC that could be exploited for novel therapeutic approaches in lung cancer therapy based on tumor ERCC1 expression.
We compared the results of repeated staining of the entire original set of samples obtained from 589 patients in the International Adjuvant Lung Cancer Trial Biology study, which had led to the initial correlation between the absence of ERCC1 expression and platinum response, with our previous results in the same tumors.
MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P=0.004-0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk.
Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02).
This meta-analysis suggests that the ERCC1 19007T>C polymorphism may be associated with lung cancer risk in Asians, while larger scale association studies are necessary to further validate the association of 19007T>C polymorphism with lung cancer risk.
These results show that the ZNF326 transcription factor is highly expressed in lung cancer and promotes the proliferation of NSCLC cells by regulating the expression of ERCC1.
Our findings suggest that rs3212986 polymorphism in 3'UTR of ERCC1 overlapped with CD3EAP may affect the repair of the damage induced by BPDE mainly via regulating ERCC1 expression and become a potential biomarker to predict smoking-related lung cancer.
Our findings suggest that rs3212986 polymorphism in 3'UTR of ERCC1 overlapped with CD3EAP may affect the repair of the damage induced by BPDE mainly via regulating ERCC1 expression and become a potential biomarker to predict smoking-related lung cancer.
Excision repair cross-complementary 1 (ERCC1) overexpression in lung cancer cells is strongly correlated with its resistance to platinum-based chemotherapy.
The ERCC1rs321986 GT and TT genotypes (at radon concentrations >200 Bq/m<sup>3</sup>) were more significantly associated with higher lung cancer risk (OR = 2.40, 95% CI = 1.29-4.45; OR = 4.45, 95% CI = 1.26-15.7, respectively).