Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilson disease (WD) is an autosomal-recessive copper overload disorder caused by mutations in the copper-transporting adenosine triphosphatase (ATPase) ATP7B. It presents with a highly variable clinical phenotype ranging from asymptomatic to fulminant hepatic failure or progressive neurological involvement. No clear genotype-phenotype correlation has been established. Thus, variants in modifier genes could have an impact on WD manifestation and severity. Recently, the antiapoptotic protein baculoviral IAP repeat-containing protein 4 BIRC4/XIAP has been suggested as a regulator of copper-induced cell death. With the aim of investigating a putative role of BIRC4/XIAP as modifier gene in individuals with copper overload, we analyzed a WD patient cohort (n = 98) for sequence variants at the BIRC4/XIAP locus. When compared with clinical data, the previously described coding single nucleotide polymorphisms (SNPs) at the BRIC4/XIAP locus (rs28382721, rs28382722, rs28382723, rs5956583, rs28382740, rs12838858, rs28382741) did not correlate with age of onset or clinical presentation in our collective. However, three previously unreported variants in the BIRC4/XIAP gene were identified (c.1-26 T > G; c.1408A > T; p.T470S; c.1019A > G; p.N340S). The two patients with variants leading to amino acid exchanges in the BIRC4/XIAP protein showed a remarkably early disease onset at the age of 5 years. Furthermore, one of these patients was only heterozygous for disease-causing mutations in the ATP7B gene. In summary, these data emphasize the need to further elucidate a role of BIRC4/XIAP variants as putative pathogenetic factors in copper overload disorders.
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PMID:Genetic analysis of BIRC4/XIAP as a putative modifier gene of Wilson disease. 2051 49

Copper-transporting P-type adenosine triphosphatase (ATP7B) is reportedly associated with platinum drug resistance in various solid tumors. However, the impact of ATP7B on platinum drug resistance in non-small cell lung cancer (NSCLC) remains unclear. We investigated in vitro cisplatin (CDDP) sensitivity using the collagen gel-droplet embedded culture drug sensitivity test. The ATP7B mRNA expression level in each specimen was also examined using real-time polymerase chain reaction. The relationship between ATP7B expression and in vitro CDDP sensitivity was then evaluated. The ATP7B mRNA expression levels in CDDP-resistant tumors were significantly higher than those in the CDDP-sensitive group (p=0.015; Mann-Whitney U test). Our results suggested that ATP7B expression is a promising chemoresistance marker for cisplatin.
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PMID:ATP7B expression is associated with in vitro sensitivity to cisplatin in non-small cell lung cancer. 2296 94

Wilson's disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder resulting from abnormal copper metabolism. Reduced copper excretion causes an excessive deposition of the copper in many organs such as the liver, central nervous system (CNS), cornea, kidney, joints, and cardiac muscle where the physiological functions of the affected organs are impaired. The underlying molecular mechanisms for WD have been extensively studied. It is now believed that a defect in P-type adenosine triphosphatase (ATP7B), the gene encoding the copper transporting P-type ATPase, is responsible for hepatic copper accumulation. Deposited copper in the liver produces toxic effects via modulating several molecular pathways. WD can be a lethal disease if left untreated. A better understanding of the molecular mechanisms causing the aberrant copper deposition and organ damage is the key to developing effective management approaches.
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PMID:Wilson's disease: a comprehensive review of the molecular mechanisms. 2580 4

Copper transporter family proteins may regulate the chemoresistance of non-small cell lung cancer (NSCLC) to platinum-based anticancer drugs. The present study aimed to investigate the expression of these proteins in lung cancer tissue specimens for association with clinicopathological data and patient responses to chemotherapy and survival. A total of 54 patients with surgically resected NSCLC that received first-line platinum-based doublet chemotherapy were recruited in the present study, and the paraffin-embedded pre-treatment tumor tissue specimens were subjected to immunohistochemical analysis for the expression of human copper transporter 1 (hCtr1) and copper-transporting p-type adenosine triphosphatase 1 (ATP7A) and 2 (ATP7B). This cohort of patients with NSCLC received platinum-based chemotherapy subsequent to the surgical removal of tumor lesions. ATP7B expression was found to be significantly associated with tumor cell differentiation, while hCtr1 expression was significantly associated with improved chemotherapeutic responses. The median survival time was 20 months in patients possessing tumors with high ATP7A expression, but >66 months in patients possessing tumors with low ATP7A expression at the end of the follow-up (P<0.001). The median survival time at the end of the follow-up was 15 months in patients with low tumor hCtr1 expression, but >66 months in patients with high tumor hCtr1 expression (P<0.001). High hCtr1 and low ATP7A expression were each favorable prognostic factors subsequent to chemotherapy for patients with resected NSCLC. Multivariate analysis revealed that high hCtr1 expression combined with low ATP7A expression, good tumor differentiation and female gender were all favorable independent predictive and prognostic factors for patients with resected NSCLC following chemotherapy. High hCtr1 expression combined with low ATP7A expression was associated with an improved prognosis in patients with resected NSCLC that received platinum-based chemotherapy. Surgery combined with neoadjuvant chemotherapy may improve the survival time of patients with NSCLC.
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PMID:Expression of the copper transporters hCtr1, ATP7A and ATP7B is associated with the response to chemotherapy and survival time in patients with resected non-small cell lung cancer. 2662 94

Copper-transporting P-type adenosine triphosphatase (ATP7B) has been identified as the pathogenic gene in hepatolenticular degeneration, or Wilson's disease (WD). The aim of this study was to explore the correlation between genetic mutations and the clinical profile of WD, and to discuss the value of mutation examination in its diagnosis for providing a scientific basis for the development of a method to examine genetic mutations. Sixty-eight Chinese Han patients with WD and 20 controls were included in this study. The ATP7B gene in DNA extracted from patient blood samples was amplified by PCR and sequenced. These sequences were compared against corresponding gene sequences obtained from healthy controls to statistically analyze the genetic mutations. Five of the nineteen mutations in ATP7B were newly detected mutations; moreover, 8 of these mutations were polymorphic (2 were newly identified). The Arg778Leu and Pro992Leu mutations in exons 8 and 13 were detected at the highest mutation frequencies of 25.74 and 16.91%, respectively. The frequencies of all other mutations were below 5%. However, the clinical manifestations of WD did not differ significantly in patients with the Arg778Leu and Pro992Leu mutations. Therefore, these mutations were considered as hotspot mutations in Chinese WD patients. However, we observed no significant correlation between these genetic types and the clinical symptoms of WD. The correlation between the mutation genotype and disease phenotype remains to be elucidated. In conclusion, the highly sensitive and specific direct DNA sequencing method can be used to screen for the causative genes of WD.
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PMID:Direct sequencing of mutations in the copper-transporting P-type adenosine triphosphate (ATP7B) gene for diagnosis and pathogenesis of Wilson's disease. 2770 81

Copper transporter 1 (CTR1), copper transporter 2 (CTR2), copper-transporting p-type adenosine triphosphatase 1 and 2 (ATP7A and ATP7B) are key mediators of cellular cisplatin, carboplatin and oxaliplatin accumulation. In this meta-analysis, we aimed to evaluate the relation of CTR1, CTR2, ATP7A and ATP7B to overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and treatment response (TR) of cancer patients who received chemotherapy based on published literatures, the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random-effect models. Subgroup analysis and sensitivity analysis were conducted; heterogeneity and publication bias were assessed. Twelve literatures and eight datasets with 2149 patients were included. Our results suggested that high CTR1 expression was associated with favorable OS, PFS, DFS and TR in cancer patients who underwent chemotherapy with acceptable heterogeneity. The relationship of CTR1 to cancer prognosis remained significant in the subgroup of patients who underwent platinum-based chemotherapy, the patients with ovarian cancer and those with lung cancer. The significance of these relationships was not influenced by geological region of publication, data origin or detection method. However, there was no evidence for relation of CTR2, ATP7A or ATP7B to OS, PFS, DFS or TR. Test of publication bias and sensitivity analysis suggested a robustness of all the summary effect estimates. In conclusion, high CTR1 level predicts prolonged survival and enhanced response to chemotherapy in cancer patients who underwent chemotherapy and CTR1 might be a potential target to circumvent chemotherapy resistance.
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PMID:The association between copper transporters and the prognosis of cancer patients undergoing chemotherapy: a meta-analysis of literatures and datasets. 2798 Feb 17


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