Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbp(pc-/-);Pten(pc+/-) mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp(-/-); Pten(+/-) and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27(KIP1), and p21(CIP1). Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbp(pc-/-);Pten(pc+/-) mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic-targeted therapy in patients with prostate cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975662 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-13-1659 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development and Validation of a Predictive Model of Prostate Screening Compliance: A Nationwide Population-Based Study.
Prostate
January 2025
Research Department, School of Medicine, Autonomous University of Sinaloa, Culiacan, México.
Introduction: Prostate cancer (PCa) is the second most common cancer in men worldwide, with significant incidence and mortality, particularly in Mexico, where diagnosis at advanced stages is common. Early detection through screening methods such as digital rectal examination and prostate-specific antigen testing is essential to improve outcomes. Despite current efforts, compliance with prostate screening (PS) remains low due to several barriers.
View Article and Find Full Text PDFAGD1/USP10/METTL13 complexes enhance cancer stem cells proliferation and diminish the therapeutic effect of docetaxel via CD44 m6A modification in castration resistant prostate cancer.
J Exp Clin Cancer Res
January 2025
Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Most patients with prostate cancer inevitably progress to castration-resistant prostate cancer (CRPC), at which stage chemotherapeutics like docetaxel become the first-line treatment. However, chemotherapy resistance typically develops after an initial period of therapeutic efficacy. Increasing evidence indicates that cancer stem cells confer chemotherapy resistance via exosomes.
View Article and Find Full Text PDFIncidence, trends and patterns of female breast, cervical, colorectal and prostate cancers in Antigua and Barbuda, 2017-2021: a retrospective study.
BMC Cancer
January 2025
Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu- Natal, Durban, South Africa.
Background: Globally, estimates of cancer cases and deaths have increased since 2018, particularly in Latin America and Caribbean countries. In Antigua and Barbuda, understanding the burden of common cancers such as female breast, cervical, colorectal and prostate cancers is critical. This study aimed to assess the incidence, trends, and patterns of these four cancers from 2017 to 2021.
View Article and Find Full Text PDFThe burden of prostate cancer in the North Africa and Middle East Region from 1990 to 2021.
Sci Rep
January 2025
Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Prostate cancer ranks among the most prevalent malignancies affecting males globally. This study sought to document the incidence, deaths and disability-adjusted life-years (DALYs) that were due to prostate cancer in the Middle East and North Africa (MENA) region, and its 21 countries, from 1990 to 2021. We analysed publicly accessible data from the Global Burden of Disease 2021 study to present findings on the incidence, deaths, and disability-adjusted life years (DALYs) associated with prostate cancer.
View Article and Find Full Text PDF[Effects of Xihuang Pills on angiogenesis, invasion, and metastasis of p rostate cancer based on FAK/Src/ERK pathway].
Zhongguo Zhong Yao Za Zhi
December 2024
Hunan Provincial Key Laboratory of Traditional Chinese Medicine Prescription and Transformation, Hunan University of Chinese Medicine Changsha 410208, China Key Laboratory of Tumor Prevention Mechanism of Traditional Chinese Medicine,Hunan University of Chinese Medicine Changsha 410208, China Key Laboratory of Traditional Chinese Medicine Tumour in Hunan Universities, Hunan University of Chinese Medicine Changsha 410208, China College of Integrative Medicine, Hunan University of Chinese Medicine Changsha 410208, China.
Based on the focal adhesion kinase(FAK)/steroid receptor coactivator(Src)/extracellular regulated protein kinase(ERK) pathway, this study explored the effects of Xihuang Pills on angiogenesis, invasion, and metastasis in prostate cancer. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to analyze and identify the active ingredients of Xihuang Pills. Bioinformatics techniques, including R language and Perl programs, were employed to analyze the interactions between prostate cancer-related targets and the potential targets of Xihuang Pills.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!