Loss of HOXC6 expression induces apoptosis in prostate cancer cells
| Autor: | So Dug Lim, Noelani Laycock, Andrew N. Young, Mahul B. Amin, Carlos S. Moreno, Fray F. Marshall, Sumathi Ramachandran, Qiqin Yin-Goen, Jeffrey K Carney, John A. Petros, Pengbo Liu |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Apoptosis Biology medicine.disease_cause Prostate cancer Internal medicine LNCaP Gene expression Genetics medicine Humans Gene silencing RNA Small Interfering Molecular Biology Transcription factor Homeodomain Proteins Regulation of gene expression Gene Expression Profiling Prostatic Neoplasms medicine.disease Gene Expression Regulation Neoplastic Gene expression profiling Insulin-Like Growth Factor Binding Protein 3 Endocrinology Cancer research Neprilysin Carcinogenesis |
| Zdroj: | Oncogene. 24:188-198 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1207906 |
| Popis: | We have performed whole genome expression profiling of 28 patient prostate tumor samples and 12 normal prostate samples and identified 55 upregulated and 60 downregulated genes significantly changed in prostate tumor samples compared to normal prostate tissues. Among the members of the upregulated gene set was the developmental transcription factor Homeobox C6 (HOXC6). Silencing of HOXC6 expression using small-interfering RNA (siRNA) resulted in decreased proliferation rates for both androgen-dependent LnCaP cells and the LnCaP-derived androgen-independent C4-2 cell line. Flow cytometry and immunoblotting for the caspase-cleaved form of poly-ADP ribose polymerase (PARP) determined that the decrease in cell numbers was due to increased apoptosis. To validate the specificity of the siRNA-induced apoptosis, LnCaP cells were cotransfected with siRNA specific to the HOXC6 3'UTR and a mammalian expression vector containing the HOXC6 open reading frame, but lacking the 3'UTR. Overexpression of HOXC6 rescued the LnCaP cells from HOXC6 siRNA-induced apoptosis, and increased growth of control GFP siRNA-transfected cells. Expression profiling of HOXC6 siRNA transfections and HOXC6 overexpression identified neutral endopeptidase (NEP) and insulin-like growth factor binding protein-3 (IGFBP-3) as potential proapoptotic repression targets of HOXC6. Our data suggest that HOXC6 may be a novel potential therapeutic target for prostate cancer. |
| Databáze: | OpenAIRE |
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