Abstract
Abstract The mechanism of human kidney cancer development is not completely understood. Recently, we have identified a new growth regulatory gene, SKCG-1 and its expression was found to be decreased or lossed in human Wilms tumor. The objective of this study was to further characterize this gene and determine whether it has growth inhibitory function in human kidney cancer. The role of DNA hypermethylation in the inhibition of SKCG-1 expression in tumorigenic kidney epithelial cells was investigated by 5′-aza-2′-deoxycytidine (demethylating agent) treatment. The role of SKCG-1 in cell growth was tested by both, silencing its expression in normal cells, and overexpressing it in tumorigenic kidney epithelial cells. Reactivation of SKCG-1 transcripts in 5′ Aza-2′-deoxycytidine -treated HEK293 cells as compared to the untreated HEK293 cells suggest the hypermethylation as one of the causes for loss of SKCG-1expression in human kidney cancer cells. Colony formation assay revealed that ectopic expression of SKCG-1 suppresses the growth of tumorigenic HEK293 cells. Small interfering RNA (siRNA)-mediated silencing of SKCG-1 in HEK293 resulted in increased cell growth and this was further confirmed by increased DNA synthesis as revealed by Brdu assay. Silencing of SKCG-1 also resulted in increased expression of cell cycle gene CyclinD1 and decreased expression of P53. Immunocytochemical staining of SKCG-1 confirmed its localization in the nuclear membrane. Immunohistochemical staining further confirmed the loss of SKCG-1 expression in human kidney tumors (RCC) and its presence in surrounding normal human kidney tissue. These results suggest that the presence of SKCG-1 inhibits the growth of cancer cells and its absence allows the growth of cancer cells. The findings of this study further support the tumor suppressor role of SKCG-1 in kidney cancer. Therefore, the restoration of SKCG-1 function and its signaling pathway(s) represents a possible therapeutic target in kidney cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5050.
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