Genome-wide gene expression profiles of clear cell renal cell carcinoma: identification of molecular targets for treatment of renal cell carcinoma.
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 down-regulation 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.
Hirota
Eiji
E
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Yan
Liang
L
Tsunoda
Tatsuhiko
T
Ashida
Shingo
S
Fujime
Makoto
M
Shuin
Taro
T
Miki
Tsuneharu
T
Nakamura
Yusuke
Y
Katagiri
Toyomasa
T
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D039961:Semaphorins / Q000037:antagonists & inhibitors / Q000235:genetics*; D015533:Transcriptional Activation
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C409766:SEMA3B protein, human; D039961:Semaphorins