ID1-, ID2-, and ID3-regulated gene expression in E2A positive or negative prostate cancer cells
| Autor: | Ananthi J. Asirvatham, Jason P.W. Carey, Jaideep Chaudhary |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Male Small interfering RNA Tumor suppressor gene Urology Blotting Western Apoptosis Cell Growth Processes Biology Transfection DU145 Cell Line Tumor Gene expression LNCaP Basic Helix-Loop-Helix Transcription Factors Humans Protein Isoforms Gene silencing Gene Silencing RNA Messenger RNA Small Interfering Cyclin-Dependent Kinase Inhibitor p16 Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction Prostatic Neoplasms Gene Expression Regulation Neoplastic Oncology Cancer research Inhibitor of Differentiation Proteins Snail Family Transcription Factors Tumor Suppressor Protein p53 Transcription Factors |
| Zdroj: | The Prostate. 67:1411-1420 |
| ISSN: | 1097-0045 0270-4137 |
| DOI: | 10.1002/pros.20633 |
| Popis: | Background The inhibitor of differentiation (Id) proteins are expressed in prostate cancer (PCA). However, there is a general lack of Id isoform-specific downstream effectors. Methods Id1, Id2, or Id3 were silenced in PCA cell lines LNCaP, DU145, and PC3 using gene-specific small interfering RNA (siRNA). The effect of Id gene silencing on representative genes involved in apoptosis (p53, SNAIL2), proliferation (p21, p16), and tumor invasion (E-cadherin and MMP9) was investigated by real-time PCR. Expression of E-proteins, the primary Id interaction partners was also evaluated to understand the molecular mechanism of action. Results The Id proteins regulated the expression of CDKNIs p16 and p21 even in the absence of E-proteins. Loss of Id1 and Id3 up- or downregulated E-cadherin expression in E-protein negative or positive PCA cell lines, respectively. The effect of Id genes on cell proliferation was also independent of CDKNIs in p16 and p21 null PC3 cells. The p53-independent anti-apoptotic effect of Id2 was mediated in part by transcriptional repressor SNAI2. MMP9 seems to be the common target of all three Id genes (Id1, Id2, and Id3). Conclusions The overall effect of Id proteins on proliferation and apoptosis is independent of E-proteins. E-proteins can however determine the magnitude of response or in some cases even reverse the Id-mediated target gene expression. Evaluating E-protein expression in conjunction with Id proteins will allow better understanding of the molecular mechanism of action of Id proteins and increase their prognostic significance in PCA. Prostate 67: 1411–1420, 2007. © 2007 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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