ArticleOncogene2004
Aberrations of the Chk2 tumour suppressor in advanced urinary bladder cancer.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells.Frontiers in pharmacology · 2024Article
- Article
- The Chk2-PKM2 axis promotes metabolic control of vasculogenic mimicry formation in p53-mutated triple-negative breast cancer.Oncogene · 2021Article
- Incidence of theCancers · 2021Article
- The Expression and Therapeutic Potential of Checkpoint Kinase 2 in Laryngeal Squamous Cell Carcinoma.Drug design, development and therapy · 2020Article
- Predictive and Prognostic Value of DNA Damage Response Associated Kinases in Solid Tumors.Frontiers in oncology · 2020Review
- Coexisting GermlineCancers · 2019Article
- 53BP1 loss induces chemoresistance of colorectal cancer cells to 5-fluorouracil by inhibiting the ATM-CHK2-P53 pathway.Journal of cancer research and clinical oncology · 2017Article
- Review
- The Expression and Clinical Outcome of pCHK2-Thr68 and pCDC25C-Ser216 in Breast Cancer.International journal of molecular sciences · 2016Article
- Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth.Cancer research · 2015Article
- Expression of DNA damage checkpoint 53BP1 is correlated with prognosis, cell proliferation and apoptosis in colorectal cancer.International journal of clinical and experimental pathology · 2015Article
- The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer.Endocrine-related cancer · 2014Review
- Article
- Nuclear localization of COX-2 in relation to the expression of stemness markers in urinary bladder cancer.Mediators of inflammation · 2012Article
- Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma.Nature communications · 2011Article
- Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study.British journal of cancer · 2008Article
- The CHEK2 gene and inherited breast cancer susceptibility.Oncogene · 2006Review
- p14ARF activates a Tip60-dependent and p53-independent ATM/ATR/CHK pathway in response to genotoxic stress.Molecular and cellular biology · 2006Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Checkpoint kinase 2 (Chk2) is a tumour suppressor and signal transducer in genome integrity checkpoints that coordinate cell-cycle progression with DNA repair or cell death in response to DNA damage. Defects of Chk2 occur in subsets of diverse sporadic malignancies and predispose to several types of hereditary carcinomas. However, the status of Chk2 in tumours of the urinary bladder remains unknown. Here, we report that among 58 advanced (grade T2-T4) human bladder carcinomas, immunohistochemical analysis revealed tumour-specific reduction or lack of Chk2 protein in 6 (10.3%) cases. Genetic analysis of the latter subset showed that a Chk2-negative carcinoma #668 harboured a truncating mutation 1100delC, in one Chk2 allele and loss of the corresponding second allele. The 1100delC mutation was also found in the germ line of this patient. Sequencing of TP53 in tumour #668 identified two missense mutations. Furthermore, the vast majority of the tumours showed 'unscheduled' activatory phosphorylation on Thr68 of Chk2 in the absence of any DNA-damaging treatment. Our results indicate that the otherwise dormant DNA damage signal transducer Chk2 is aberrantly and constitutively activated in invasive urinary bladder carcinomas, and that such likely proapoptotic checkpoint signalling can be disabled by inactivation of Chk2 and/or p53 tumour suppressors in subsets of these tumours.
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