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.
