ArticleFree radical biology & medicine2012
Reactive oxygen species induced by p66Shc longevity protein mediate nongenomic androgen action via tyrosine phosphorylation signaling to enhance tumorigenicity of prostate cancer cells.
Article in Free radical biology & medicine, 2012. 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, 30 citations in OpenAlex.
- The Role of p66Shc in Cancer: Molecular Mechanisms and Therapeutic Implications.Journal of cellular and molecular medicine · 2025Review
- Association of Dietary Antioxidant Potential with Sarcopenia in Hypertension.Reviews in cardiovascular medicine · 2025Article
- Revisiting HER2 in Prostate Cancer from an Inclusive Perspective: From Biomarkers to Omics.Cancers · 2024Review
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress.Redox biology · 2024Article
- Dynamics of antioxidant heme oxygenase-1 and pro-oxidant p66Shc in promoting advanced prostate cancer progression.Free radical biology & medicine · 2022Article
- Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer.BioMed research international · 2020Review
- p66Shc protein through a redox mechanism enhances the progression of prostate cancer cells towards castration-resistance.Free radical biology & medicine · 2019Article
- ErbB-2 signaling in advanced prostate cancer progression and potential therapyEndocrine-related cancer · 2019Review
- p66Shc regulates migration of castration-resistant prostate cancer cells.Cellular signalling · 2018Article
- Effects of Resveratrol on p66Shc phosphorylation in cultured prostate cells.Translational medicine @ UniSa · 2015Article
- ErbB-2 signaling plays a critical role in regulating androgen-sensitive and castration-resistant androgen receptor-positive prostate cancer cells.Cellular signalling · 2015Article
- p66Shc longevity protein regulates the proliferation of human ovarian cancer cells.Molecular carcinogenesis · 2015Article
- p66Shc as a switch in bringing about contrasting responses in cell growth: implications on cell proliferation and apoptosis.Molecular cancer · 2015Review
- Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.Cancer letters · 2014Article
- Cellular prostatic acid phosphatase, a PTEN-functional homologue in prostate epithelia, functions as a prostate-specific tumor suppressor.Biochimica et biophysica acta · 2014Review
- Regulation of the pentose phosphate pathway by an androgen receptor-mTOR-mediated mechanism and its role in prostate cancer cell growth.Oncogenesis · 2014Article
- The adaptor proteins p66Shc and Grb2 regulate the activation of the GTPases ARF1 and ARF6 in invasive breast cancer cells.The Journal of biological chemistry · 2014Article
- Androgens promote prostate cancer cell growth through induction of autophagy.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Transmembrane prostatic acid phosphatase (TMPAP) interacts with snapin and deficient mice develop prostate adenocarcinoma.PloS one · 2013Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Steroid hormones exhibit diverse biological activities. Despite intensive studies on steroid function at the genomic level, their nongenomic actions remain an enigma. In this study, we investigated the role of reactive oxygen species (ROS) in androgen-stimulated prostate cancer (PCa) cell proliferation. In androgen-treated PCa cells, increased cell growth and ROS production correlated with elevated p66Shc protein, an authentic oxidase. This growth stimulation was blocked by antioxidants. Further, elevated expression of p66Shc protein by cDNA transfection encoding wild-type protein, but not a redox-deficient (W134F) mutant, was associated with increased PCa cell proliferation. Conversely, knockdown of p66Shc expression by shRNA resulted in diminished cell growth. Increased p66Shc expression in PCa cells enhanced their tumorigenicity in xenograft animals. Importantly, p66Shc protein level is higher in clinical prostate adenocarcinomas than in adjacent noncancerous cells. Expression of redox-deficient p66Shc mutant protein abolished androgen-stimulated cell growth. In androgen-treated, H(2)O(2)-treated, and p66Shc cDNA-transfected PCa cells, cellular prostatic acid phosphatase, an authentic tyrosine phosphatase, was inactivated by reversible oxidation; subsequently, ErbB-2 was activated by phosphorylation at tyrosine-1221/1222. These results together support the notion that androgens induce ROS production through the elevation of p66Shc protein, which inactivates tyrosine phosphatase activity for the activation of interacting tyrosine kinase, leading to increased cell proliferation and enhanced tumorigenicity. Our results thus suggest that p66Shc protein functions at the critical junction point between androgens and tyrosine phosphorylation signaling in human PCa cells.
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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.