ArticleNeoplasia (New York, N.Y.)2014
Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts.
Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- Article
- Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness.Science advances · 2023Article
- DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities.Experimental & molecular medicine · 2022Review
- High Expression of RECQL Protein in ER-Positive Breast Tumours Is Associated With a Better Survival.Frontiers in oncology · 2022Article
- Article
- XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib.Therapeutic advances in medical oncology · 2020Article
- Prognostic relevance of ATM protein in uveal melanoma and its association with clinicopathological factors.International journal of clinical oncology · 2019Article
- High-level expression of protein tyrosine phosphatase non-receptor 12 is a strong and independent predictor of poor prognosis in prostate cancer.BMC cancer · 2019Article
- Clinicopathological significance of ataxia telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3-related (ATR) kinase in MYC overexpressed breast cancers.Breast cancer research and treatment · 2019Article
- Molecular features unique to glioblastoma radiation resistant residual cells may affect patient outcome - a short report.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients withJournal of breast cancer · 2018Article
- ATM in breast and brain tumors: a comprehensive review.Cancer biology & medicine · 2018Article
- Article
- CD44Oncology letters · 2017Article
- WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation.Cell research · 2017Article
- Clinicopathological and Functional Significance of RECQL1 Helicase in Sporadic Breast Cancers.Molecular cancer therapeutics · 2017Article
- Article
- The Expression and Clinical Outcome of pCHK2-Thr68 and pCDC25C-Ser216 in Breast Cancer.International journal of molecular sciences · 2016Article
- ATM protein is deficient in over 40% of lung adenocarcinomas.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1950). Low nuclear ATM protein level was significantly associated with aggressive breast cancer including larger tumors, higher tumor grade, higher mitotic index, pleomorphism, tumor type, lymphovascular invasion, estrogen receptor (ER)-, PR -, AR -, triple-negative, and basal-like phenotypes (Ps < .05). Breast cancer 1, early onset negative, low XRCC1, low SMUG1, high FEN1, high MIB1, p53 mutants, low MDM2, low Bcl-2, low p21, low Bax, high CDK1, and low Chk2 were also more frequent in tumors with low nuclear ATM level (Ps < .05). Low ATM protein level was significantly associated with poor survival including in patients with ER-negative tumors who received adjuvant anthracycline or cyclophosphamide, methotrexate, and 5-fluorouracil-based adjuvant chemotherapy (Ps < .05). Low nuclear Chk2 protein was likely in ER -/PR -/AR -; HER-2 positive; breast cancer 1, early onset negative; low XRCC1; low SMUG1; low APE1; low polβ; low DNA-PKcs; low ATM; low Bcl-2; and low TOPO2A tumors (P < .05). In patients with ER + tumors who received endocrine therapy or ER-negative tumors who received chemotherapy, nuclear Chk2 levels did not significantly influence survival. In p53 mutant tumors, low ATM (P < .000001) or high Chk2 (P < .01) was associated with poor survival. When investigated together, low-ATM/high-Chk2 tumors have the worst survival (P = .0033). Our data suggest that ATM-Chk2 levels in sporadic breast cancer may have prognostic and predictive significance.
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