Reaching for the star. (c2011)

Abstract

Astrocytomas are tumors occurring in young adulthood. Astrocytic tumors can be classified into four grades according to histologic features: grade I, grade II, grade III and grade IV. Malignant tumors, those of grade III and IV, are characterized by uncontrolled proliferation, which is known to be regulated by the family of Rho GTPases. StarD13, a GAP for Rho GTPases, has been described as a tumor suppressor in hepatocellular carcinoma. In the present study, IHC analysis on Grade I-IV brain tissues from patients showed StarD13 to be overexpressed in grade III and IV astrocytoma tumors when compared to grade I and II. However, when we mined the REMBRANDT data, we found that the mRNA levels of StarD13 are indeed higher in the higher grades but much lower than the normal tissues. The overexpression of a GFP-StarD13 construct in astrocytoma cells led to the increase in cell death and a decrease of cell viability. Knocking down StarD13 using siRNA led to a decrease in cell death and an increase in cell viability. When looking at the mechanism, we found that the tumor suppressor effect of StarD13 is through the inhibition of the cell cycle and not through the activation of apoptosis. When knocking down StarD13, we also saw an increase in p-ERK, uncovering a potential link between Rho GTPases and ERK activation. Our future interests would be to determine which Rho GTPase is responsible for this effect and to elucidate the direct link between the Rho GTPase and ERK.