Research On The Functions Of Rap2 In Renal Carcinogenesis

Rap2 is a Ras family G protein showing 60% amino acid similarity to Rap1 which was firstly identified as a transformation suppressor against the oncogenic Ki-Ras. Although the roles of Rap1 in several cell processes including cell adhesion, cell polarity, cell proliferation and differentiation were described recently, the biological roles of Rap2 are still unclear. The identification of several novel targets specific for Rap2 has suggested that Rap2 could play quite different roles other than Rap1. In the study, the oncogenic properties of Rap2 were assessed. First, HEK293 cells stably expressing Rap2, Rap1 or Rap1-12V were established, and the in vitro and in vivo growth properties were detected. Although the anchorage-dependent cell growth was not changed significantly by the expression of Rap2 as shown by the growth curve, the anchorage-independent cell growth were largely increased in the cells expressing Rap2 as characterized by the enhanced ability to form colonies in soft agar, suggesting that Rap2 expression promoted the cell transformation. Furthermore, the spreading of HEK293 cells induced by R-Ras-38V, C3G-CAAX or Rap1-63E was significantly inhibited by the expression of Rap2, suggesting that Rap2 may promote cell migration through eliminating the interactions of cell-ECM. The tumorigenity of HEK293 cells expressing Rap2 were assayed in nude mice, and the HEK293 cells expressing Rap2 showed stronger tumorigenic ability than any of the control cells. Results suggest that Rap2 may serve as a proto-oncogene implicated in the renal carcinogenesis.