Inhibitor of differentiation 4 (Id4) is a potential tumor suppressor in prostate cancer
| Autor: | Jaideep Chaudhary, Oliver Galm, Jason P.W. Carey, Tandeih A Ghogomu, Ananthi J. Asirvatham |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Male
Cancer Research Down-Regulation Apoptosis Cell Growth Processes Biology Transfection lcsh:RC254-282 03 medical and health sciences Prostate cancer 0302 clinical medicine DU145 Cell Line Tumor medicine Genetics Humans Genes Tumor Suppressor Promoter Regions Genetic Transcription factor 030304 developmental biology Regulation of gene expression 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Cell Cycle Cancer Prostatic Neoplasms Cell cycle DNA Methylation lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Molecular biology Androgen receptor Gene Expression Regulation Neoplastic Oncology Receptors Androgen 030220 oncology & carcinogenesis DNA methylation Cancer research Inhibitor of Differentiation Proteins Research Article |
| Zdroj: | BMC Cancer BMC Cancer, Vol 9, Iss 1, p 173 (2009) |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-9-173 |
| Popis: | Background Inhibitor of differentiation 4 (Id4), a member of the Id gene family is also a dominant negative regulator of basic helix loop helix (bHLH) transcription factors. Some of the functions of Id4 appear to be unique as compared to its other family members Id1, Id2 and Id3. Loss of Id4 gene expression in many cancers in association with promoter hypermethylation has led to the proposal that Id4 may act as a tumor suppressor. In this study we provide functional evidence that Id4 indeed acts as a tumor suppressor and is part of a cancer associated epigenetic re-programming. Methods Data mining was used to demonstrate Id4 expression in prostate cancer. Methylation specific polymerase chain reaction (MSP) analysis was performed to understand molecular mechanisms associated with Id4 expression in prostate cancer cell lines. The effect of ectopic Id4 expression in DU145 cells was determined by cell cycle analysis (3H thymidine incorporation and FACS), expression of androgen receptor, p53 and cyclin dependent kinase inhibitors p27 and p21 by a combination of RT-PCR, real time-PCR, western blot and immuno-cytochemical analysis. Results Id4 expression was down-regulated in prostate cancer. Id4 expression was also down-regulated in prostate cancer line DU145 due to promoter hyper-methylation. Ectopic Id4 expression in DU145 prostate cancer cell line led to increased apoptosis and decreased cell proliferation due in part by an S-phase arrest. In addition to S-phase arrest, ectopic Id4 expression in PC3 cells also resulted in prolonged G2/M phase. At the molecular level these changes were associated with increased androgen receptor (AR), p21, p27 and p53 expression in DU145 cells. Conclusion The results suggest that Id4 acts directly as a tumor suppressor by influencing a hierarchy of cellular processes at multiple levels that leads to a decreased cell proliferation and change in morphology that is possibly mediated through induction of previously silenced tumor suppressors. |
| Databáze: | OpenAIRE |
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