Table of Contents
Molecular Biology International
Volume 2012, Article ID 705948, 8 pages
Research Article

Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy

Molecular Targets Program, Department of Medicine, James Graham Brown Cancer Center, University of Louisville, 505 S. Hancock Street, Louisville, KY 40202, USA

Received 9 February 2012; Accepted 27 March 2012

Academic Editor: Farida Latif

Copyright © 2012 Jennifer Clark et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.