ERCC1 Expression in Non-Small Cell Lung and Esophageal Cancer

Bilen, Nurhan; Tekin, Salim Başol; Topdağı, Ömer

doi:10.5152/eajm.2014.21

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…High expression of XP genes, like ERCC1 , has also been correlated with poor therapy response in different cancer entities like e.g. non-small cell lung cancer, esophageal cancer, breast cancer, colorectal cancer, as well as head and neck cancer [ 58 – 61 ]. Testes tumors with reduced levels of NER proteins could be cured after application of a cisplatin-based therapy, even though they were already in an advanced metastasizing state.…”

Section: Discussionmentioning

confidence: 99%

Splice variants of the endonucleases XPF and XPG contain residual DNA repair capabilities and could be a valuable tool for personalized medicine

Lehmann

Schubert²,

Seebode

et al. 2017

Oncotarget

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The two endonucleases XPF and XPG are essentially involved in nucleotide excision repair (NER) and interstrand crosslink (ICL) repair. Defects in these two proteins result in severe diseases like xeroderma pigmentosum (XP). We applied our newly CRISPR/Cas9 generated human XPF knockout cell line with complete loss of XPF and primary fibroblasts from an XP-G patient (XP20BE) to analyze until now uncharacterized spontaneous mRNA splice variants of these two endonucleases. Functional analyses of these variants were performed using luciferase-based reporter gene assays. Two XPF and XPG splice variants with residual repair capabilities in NER, as well as ICL repair could be identified. Almost all variants are severely C-terminally truncated and lack important protein-protein interaction domains. Interestingly, XPF-202, differing to XPF-003 in the first 12 amino acids only, had no repair capability at all, suggesting an important role of this region during DNA repair, potentially concerning protein-protein interaction. We also identified splice variants of XPF and XPG exerting inhibitory effects on NER. Moreover, we showed that the XPF and XPG splice variants presented with different inter-individual expression patterns in healthy donors, as well as in various tissues. With regard to their residual repair capability and dominant-negative effects, functionally relevant spontaneous XPF and XPG splice variants present promising prognostic marker candidates for individual cancer risk, disease outcome, or therapeutic success. This merits further investigations, large association studies, and translational research within clinical trials in the future.

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Section: Discussionmentioning

confidence: 99%

Splice variants of the endonucleases XPF and XPG contain residual DNA repair capabilities and could be a valuable tool for personalized medicine

Lehmann

Schubert²,

Seebode

et al. 2017

Oncotarget

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“…Excision repair cross-complementary gene 1 (ERCC1) and breast cancer susceptibility gene 1 (BRCA1) are important members of the DNA repair-related gene system [ 9 , 10 ]. Studies showed that they can reflect the sensitivity to chemotherapy drugs, and their overexpression can affect the clinical curative effect of chemotherapy drugs in NSCLC [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

DNA Repair Genes ERCC1 and BRCA1 Expression in Non-Small Cell Lung Cancer Chemotherapy Drug Resistance

et al. 2016

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BackgroundSurgery combined with chemotherapy is an important therapy for non-small cell lung cancer (NSCLC). However, chemotherapy drug resistance seriously hinders the curative effect. Studies show that DNA repair genes ERCC1 and BRCA1 are associated with NSCLC chemotherapy, but their expression and mechanism in NSCLC chemotherapy drug-resistant cells has not been elucidated.Material/MethodsNSCLC cell line A549 and drug resistance cell line A549/DDP were cultured. Real-time PCR and Western blot analyses were used to detect ERCC1 and BRCA1 mRNA expression. A549/DDP cells were randomly divided into 3 groups: the control group; the siRNA-negative control group (scramble group); and the siRNA ERCC1 and BRCA1siRNA transfection group. Real-time PCR and Western blot analyses were used to determine ERCC1 and BRCA1 mRNA and protein expression. MTT was used to detect cell proliferation activity. Caspase 3 activity was tested by use of a kit. Western blot analysis was performed to detect PI3K, AKT, phosphorylated PI3K, and phosphorylated AKT protein expression.ResultsERCC1 and BRCA1 were overexpressed in A549/DDP compared with A549 (P<0.05). ERCC1 and BRCA1siRNA transfection can significantly reduce ERCC1 and BRCA1 mRNA and protein expression (P<0.05). Downregulating ERCC1 and BRCA1 expression obviously inhibited cell proliferation and increased caspase 3 activity (P<0.05). Downregulating ERCC1 and BRCA1 significantly decreased PI3K and AKT phosphorylation levels (P<0.05).ConclusionsERCC1 and BRCA1 were overexpressed in NSCLC drug-resistant cells, and they regulated lung cancer occurrence and development through the phosphorylating PI3K/AKT signaling pathway.

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“…Lung carcinoma is the leading cause of cancer death among men and the second leading cause of cancer death among women worldwide . Chest radiography is the first method of choice for imaging evaluation of lung carcinoma.…”

mentioning

confidence: 99%

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results

Karaman

Durur-Subasi

Alper

et al. 2017

Magnetic Resonance Imaging

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ERCC1 Expression in Non-Small Cell Lung and Esophageal Cancer

Cited by 3 publications

References 12 publications

Splice variants of the endonucleases XPF and XPG contain residual DNA repair capabilities and could be a valuable tool for personalized medicine

Splice variants of the endonucleases XPF and XPG contain residual DNA repair capabilities and could be a valuable tool for personalized medicine

DNA Repair Genes ERCC1 and BRCA1 Expression in Non-Small Cell Lung Cancer Chemotherapy Drug Resistance

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results

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