ArticlePloS one2012
Inactivation of ATM/ATR DNA damage checkpoint promotes androgen induced chromosomal instability in prostate epithelial cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting Prostate Cancer, the 'Tousled Way'.International journal of molecular sciences · 2023Review
- Article
- BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations.International journal of molecular sciences · 2021Review
- SPOP Deregulation Improves the Radiation Response of Prostate Cancer Models by Impairing DNA Damage Repair.Cancers · 2020Article
- Targeting the TLK1/NEK1 DDR axis with Thioridazine suppresses outgrowth of androgen independent prostate tumors.International journal of cancer · 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
- IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting.Nature communications · 2017Article
- Metabolism of the Tobacco Carcinogen 2-Amino-9H-pyrido[2,3-b]indole (AαC) in Primary Human Hepatocytes.Chemical research in toxicology · 2017Article
- Research Resource: Androgen Receptor Activity Is Regulated Through the Mobilization of Cell Surface Receptor Networks.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory.Molecular neurobiology · 2015Article
- Topoisomerase-mediated chromosomal break repair: an emerging player in many games.Nature reviews. Cancer · 2015Review
- Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression.BMC medical genetics · 2014Article
- The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer.Endocrine-related cancer · 2014Review
- Androgen receptor and gene network: Micromechanics reassemble the signaling machinery of TMPRSS2-ERG positive prostate cancer cells.Cancer cell international · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer. However, whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown. Here, we show that exposure of non-malignant prostate epithelial cells (HPr-1AR) to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence. Notably, knockdown of the ATM gene expression in HPr-1AR cells can promote androgen-induced TMPRSS2: ERG rearrangement, a prostate-specific chromosome translocation frequently found in prostate cancer cells. Intriguingly, unlike the non-malignant prostate epithelial cells, the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells, since androgen treatment only induced a partial activation of the DNA damage response. This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX, lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway. Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.