MYC pathway is activated in clear cell renal cell carcinoma and essential for proliferation of clear cell renal cell carcinoma cells
| Autor: | Wei-Chou Lin, Sai-Wen Tang, Jung-Yaw Lin, Chyong-Ing Hsu, Yu-Chi Chen, Ming-Kuen Lai, Yih-Ching Su, Wen-Hsin Chang, Yen-Han Lai, Pei-Tzu Wu |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Blotting Western Proto-Oncogene Proteins c-myc Cyclin D1 Downregulation and upregulation Cell Line Tumor medicine Humans Carcinoma Renal Cell Cell Proliferation Gene knockdown biology Reverse Transcriptase Polymerase Chain Reaction Cell cycle medicine.disease Immunohistochemistry Kidney Neoplasms Up-Regulation Proliferating cell nuclear antigen Gene Expression Regulation Neoplastic Clear cell renal cell carcinoma Oncology Cell culture biology.protein Cancer research RNA Interference Chromatin immunoprecipitation Signal Transduction |
| Zdroj: | Cancer Letters. 273:35-43 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2008.07.038 |
| Popis: | Clear cell renal cell carcinoma (ccRCC) is the major and aggressive subtype of RCC. Previously, we identified 383 differentially expressed genes by analyzing full-length cDNA libraries of ccRCC and normal kidney tissues. In this study, we applied functional network analysis to the differentially expressed genes for identifying deregulated molecular pathways in ccRCC, and the results indicated that MYC showed a prominent role in the highest scoring network. The upregulation of MYC expression was validated in ccRCC tissues and cell lines. Furthermore, Knockdown of MYC expression by MYC-specific siRNA significantly inhibited the abilities of uncontrolled proliferation, anchorage-independent growth and arrested cell cycle in the G0/G1 phase in ccRCC cells. Moreover, we found that 37 differentially expressed genes were shown to be MYC-target genes, and the upregulation of the MYC-target genes BCL2, CCND1, PCNA, PGK1, and VEGFA were demonstrated. The expression of these MYC-target genes was significantly correlated with the expression of MYC in ccRCC tissues, and knockdown of MYC also suppressed the expression of these MYC-target genes in ccRCC cells. The recruitment of MYC to the promoter regions of BCL2, CCND1, PCNA, PGK1, and VEGFA was shown by Chromatin immunoprecipitation assay. These results suggest that MYC pathway is activated and plays an essential role in the proliferation of ccRCC cells. |
| Databáze: | OpenAIRE |
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