Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen

Parafibromin is a 531-amino acid protein encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal dominant hyperparathyroidism-jaw tumor familial cancer syndrome and sporadic parathyroid carcinoma. To investigate effects of parafibromin's overexpression on cell proliferation, we performed assays in four different cell lines. The transient overexpression of parafibromin inhibited cell growth in HEK293 and NIH3T3 cells, but enhanced cell growth in the SV40 large T antigen expressing-cell lines such as 293FT and COS7 cells. In 293FT cells, parafibromin was found to interact with SV40 large T antigen and its overexpression promoted entry into the S phase, implying that the interaction enhanced progression through the cell cycle. The tumor suppressor protein parafibromin acts as a positive regulator of cell growth like an oncoprotein in the presence of SV40 large T antigen.