Genome-wide gene expression profiles of clear cell renal cell carcinoma: Identification of molecular targets for treatment of renal cell carcinoma

Abstract

In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes. We identified 257 genes that were commonly up-regulated and 721 genes that were down-regulated in RCCs. None of top 24 up-regulated genes that showed most significant differences in informative RCC-cases were included in previous reports describing expression profiles of RCC using RNAs isolated from bulk tissues. These findings suggest that it is important to purify as much as possible the populations of cancerous and normal epithelial cells obtained from surgical specimens. Among the significantly-transactivated genes, we focused on Semaphorin 5B (SEMA5B) and knocked-down its expression in RCC cells by small-interfering RNA (siRNA). Effective downregulation of its expression levels in RCC cells significantly attenuated RCC cell viability. In conclusion, our data should be helpful for a better understanding of the tumorigenesis of RCC and should contribute to the development of diagnostic tumor markers and molecular-targeting therapy for patients with RCC.

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

“…After amplified RNAs (aRNAs) were labeled with Cy3 or Cy5, respectively, we carried out hybridization between labeled aRNAs and cDNA microarray slides containing 36 864 spots and detected the signals. Expression of CDC20 in various cancer tissues and their corresponding normal tissues were examined by using data sets that were analysed previously (Ono et al, 2000;Kitahara et al, 2001;Okabe et al, 2001;Hasegawa et al, 2002;Kaneta et al, 2002;Kitahara et al, 2002;Nagayama et al, 2002;Okutsu et al, 2002;Kikuchi et al, 2003;Okada et al, 2003;Ashida et al, 2004;Jinawath et al, 2004;Nakamura et al, 2004;Nishidate et al, 2004;Ochi et al, 2004;Obama et al, 2005;Takata et al, 2005;Hirota et al, 2006;Taniwaki et al, 2006;Yamabuki et al, 2006). To select genes that were suppressed by p53 and upregulated in various cancer tissues, the following two criteria were used: (1) genes whose expression were more than threefold decreased by Ad-p53 and (2) genes whose expression were more than threefold increased in various cancer tissues compared with its corresponding normal tissues.…”

DDX31 Regulates the p53-HDM2 Pathway and rRNA Gene Transcription through Its Interaction with NPM1 in Renal Cell Carcinomas

“…The extraction of total RNA from cultured cells and RCC clinical tissues, reverse transcription, and subsequent PCR amplification were conducted as previously described (20). b-Actin was used as a quantitative control.…”

“…To this end, we analyzed the expression profiling of clear cell RCC (ccRCC), which is a major histologic type of RCC (the Gene Expression Omnibus database accession number: GSE39364; ref. 20), and identified and characterized DEAD (Asp-Glu-Ala-Asp) box polypeptide 31 (DDX31), a novel member of the DEAD box protein family.…”

Involvement of C12orf32 overexpression in breast carcinogenesis

“…Through the genome-wide expression analysis of a large number of microdissected clinical cancer materials, we have identified dozens of genes that function as oncogenes in the process of development and/or progression of breast cancer (10)(11)(12)(13)(14)(15)(16)(17), bladder cancer (18,19), synovial sarcoma (20,21), testicular seminoma (22), and renal cell carcinoma (23,24). Such molecules are considered to be candidate molecular targets for development of new therapeutic modalities.…”