In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for development of novel treatments of renal cell carcinoma (RCC), we previously analyzed genome-wide gene expression profiles of clear-cell types of RCC by cDNA microarray. Among the transcativated genes, we herein focused on functional significance of TMEM22 (transmembrane protein 22), a transmembrane protein, in cell growth of RCC. Northern blot and semi-quantitative RT-PCR analyses confirmed up-regulation of TMEM22 in a great majority of RCC clinical samples and cell lines examined. Immunocytochemical analysis validated its localization at the plasma membrane. We found an interaction between TMEM22 and RAB37 (Ras-related protein Rab-37), which was also up-regulated in RCC cells. Interestingly, knockdown of either of TMEM22 or RAB37 expression by specific siRNA caused significant reduction of cancer cell growth. Our results imply that the TMEM22/RAB37 complex is likely to play a crucial role in growth of RCC and that inhibition of the TMEM22/RAB37 expression or their interaction should be novel therapeutic targets for RCC.

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