MYC pathway is activated in clear cell renal cell carcinoma and essential for proliferation of clear cell renal cell carcinoma cells

• Published in: Cancer letters 2009-01, Vol.273 (1), p.35-43
• Main Authors: Tang, Sai-Wen, Chang, Wen-Hsin, Su, Yih-Ching, Chen, Yu-Chi, Lai, Yen-Han, Wu, Pei-Tzu, Hsu, Chyong-Ing, Lin, Wei-Chou, Lai, Ming-Kuen, Lin, Jung-Yaw
• Format: Article
• Language: English
• Subjects: Activation of MYC pathway; Angiogenesis; Apoptosis; Blotting, Western; Cancer; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - physiopathology; Cell culture; Cell cycle; Cell Line, Tumor; Cell Proliferation; Clear cell renal cell carcinoma; Full-length cDNA library; Gene expression; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - physiopathology; Kinases; Knockdown of MYC; Lymphoma; Medical prognosis; Phase transitions; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Reproductive system; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA polymerase; Rodents; Signal Transduction; Up-Regulation; Vascular endothelial growth factor
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2008.07.038

Abstract 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.