RhoGAP DLC-1 tumor suppression and aberrant Rho GTPase activation in lung cancer

摘要: 4125 The deleted in liver cancer-1 (DLC-1) gene was originally identified as a tumor suppressor whose expression lost hepatocellular carcinomas. Subsequently, reduced of DLC-1 mRNA reported breast, colon, prostate, gastric, and lung cancers, with transcript 95% primary non-small cell carcinomas (NSCLC) nearly 60% NSCLC lines. encodes RhoGAP domain (GTPase activating protein for Rho family small GTPases) that is hypothesized to be responsible the tumor-suppressor function DLC-1. In vitro studies have demonstrated inactivates GTPase RhoA by catalyzing GTP hydrolysis activity. However, whether consequence inhibition RhoA, activation important aberrant growth NSCLCs not been determined. We performed western blot analysis on panel six lines, A549, H23, H358, H2228 cells. Ectopic restoration deficient lines resulted proliferation plastic well anchorage-independent growth. Pull down analyses GTP-binding fragment effector Rhotekin has shown results RhoA-GTP levels vivo . also utilized short interfering RNA (siRNA) knockdown endogenous positive are currently assessing impact transforming properties signaling pathways these