ArticleMolecular oncology2016
DNA damage signalling barrier, oxidative stress and treatment-relevant DNA repair factor alterations during progression of human prostate cancer.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
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- Contemporary review of prognostic markers of prostate cancer from a pathologist perspective.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025Review
- It's a match: use of the radionuclide theranostic pairEJNMMI radiopharmacy and chemistry · 2025Article
- Deletions ofBiomolecules · 2025Article
- New biomarkers and multiplex tests for diagnosis of aggressive prostate cancer and therapy management.Frontiers in oncology · 2025Review
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- Epigenetic roles of KDM3B and KDM3C in tumorigenesis and their therapeutic implications.Cell death & disease · 2024Review
- Predictive tissue markers in testicular germ cell tumors: Immunohistochemical expression of MLH1 and REV-7 proteins.International urology and nephrology · 2024Article
- The Immunohistochemical Expression of REV-7 in Various Human Cancer Pathology Specimens: A Systematic Review.Cureus · 2024Review
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- Expression differences between proteins responsible for DNA damage repair according to the Gleason grade as a new heterogeneity marker in prostate cancer.Archives of medical science : AMS · 2023Article
- Modulating the pharmacokinetic profile of Actinium-225-labeled macropa-derived radioconjugates by dual targeting of PSMA and albumin.Theranostics · 2022Article
- Anti-proliferative and apoptotic effects of hull-less pumpkin extract on human papillary thyroid carcinoma cell line.Anatomy & cell biology · 2021Article
- Lung toxicity and gene expression changes in response to whole-body inhalation exposure to cellulose nanocrystal in rats.Inhalation toxicology · 2021Article
- Differential DNA Methylation in Prostate Tumors from Puerto Rican Men.International journal of molecular sciences · 2021Article
- Article
- Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility.Antioxidants (Basel, Switzerland) · 2020Review
- Attenuation of NAD[P]H:quinone oxidoreductase 1 aggravates prostate cancer and tumor cell plasticity through enhanced TGFβ signaling.Communications biology · 2020Article
- NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma.Cell communication and signaling : CCS · 2019Article
- Possible anti-oxidative effects of long-term administration of Juzen-taiho-to in dogs.The Journal of veterinary medical science · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The DNA damage checkpoints provide an anti-cancer barrier in diverse tumour types, however this concept has remained unexplored in prostate cancer (CaP). Furthermore, targeting DNA repair defects by PARP1 inhibitors (PARPi) as a cancer treatment strategy is emerging yet requires suitable predictive biomarkers. To address these issues, we performed immunohistochemical analysis of multiple markers of DNA damage signalling, oxidative stress, DNA repair and cell cycle control pathways during progression of human prostate disease from benign hyperplasia, through intraepithelial neoplasia to CaP, complemented by genetic analyses of TMPRSS2-ERG rearrangement and NQO1, an anti-oxidant factor and p53 protector. The DNA damage checkpoint barrier (γH2AX, pATM, p53) mechanism was activated during CaP tumorigenesis, albeit less and with delayed culmination compared to other cancers, possibly reflecting lower replication stress (slow proliferation despite cases of Rb loss and cyclin D1 overexpression) and progressive loss of ATM activator NKX3.1. Oxidative stress (8-oxoguanine lesions) and NQO1 increased during disease progression. NQO1 genotypes of 390 men did not indicate predisposition to CaP, yet loss of NQO1 in CaP suggested potential progression-opposing tumour suppressor role. TMPRSS2-ERG rearrangement and PTEN loss, events sensitizing to PARPi, occurred frequently along with heterogeneous loss of DNA repair factors 53BP1, JMJD1C and Rev7 (all studied here for the first time in CaP) whose defects may cause resistance to PARPi. Overall, our results reveal an unorthodox DNA damage checkpoint barrier scenario in CaP tumorigenesis, and provide novel insights into oxidative stress and DNA repair, with implications for biomarker guidance of future targeted therapy of CaP.
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