Tumor Suppressor Properties of Small C-Terminal Domain Phosphatases in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) accounts for 80-90% of kidney cancers worldwide. Small C-terminal domain phosphatases CTDSP1, CTDSP2, and CTDSPL (also known as SCP1, 2, 3) are involved in the regulation of several important pathways associated with carcinogenesis. In various cancer types, these phosphatases may demonstrate either antitumor or oncogenic activity. Tumor-suppressive activity of these phosphatases in kidney cancer has been shown previously, but in general case, the antitumor activity may be dependent on the choice of cell line. In the present work, transfection of the Caki-1 cell line (ccRCC morphologic phenotype) with expression constructs containing the coding regions of these genes resulted in inhibition of cell growth in vitro in the case of ( < 0.001) and ( < 0.05) but not . The analysis of The Cancer Genome Atlas (TCGA) data showed differential expression of some of genes and of their target, . These results were confirmed by quantitative RT-PCR using an independent sample of primary ccRCC tumors ( = 52). We observed downregulation and found a positive correlation of expression for two gene pairs: and ( = 0.76; < 0.001) and and ( = 0.38; < 0.05). Survival analysis based on TCGA data demonstrated a strong association of lower expression of , , , and with poor survival of ccRCC patients ( < 0.001). In addition, according to TCGA, , , and were differently expressed in two subtypes of ccRCC-ccA and ccB, characterized by different survival rates. These results confirm that and have tumor suppressor properties in ccRCC and reflect their association with the more aggressive ccRCC phenotype.