Table of Contents
Molecular Biology International
Volume 2013 (2013), Article ID 145096, 9 pages
http://dx.doi.org/10.1155/2013/145096
Research Article

The RASSF1 Gene and the Opposing Effects of the RASSF1A and RASSF1C Isoforms on Cell Proliferation and Apoptosis

1Surgical Oncology Laboratory, Loma Linda VA Medical Center, Loma Linda, CA 92357, USA
2Department of Surgery, Loma Linda University, Loma Linda, CA 92357, USA
3Musculoskeletal Disease Center, Loma Linda VA Medical Center, Loma Linda, CA 92357, USA

Received 22 July 2013; Accepted 25 September 2013

Academic Editor: Emanuel Strehler

Copyright © 2013 Mark E. Reeves 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.

Abstract

RASSF1A has been demonstrated to be a tumor suppressor, while RASSF1C is now emerging as a growth promoting protein in breast and lung cancer cells. To further highlight the dual functionality of the RASSF1 gene, we have compared the effects of RASSF1A and RASSF1C on cell proliferation and apoptosis in the presence of TNF-α. Overexpression of RASSF1C in breast and lung cancer cells reduced the effects of TNF-α on cell proliferation, apoptosis, and MST1/2 phosphorylation, while overexpression of RASSF1A had the opposite effect. We also assessed the expression of RASSF1A and RASSF1C in breast and lung tumor and matched normal tissues. We found that RASSF1A mRNA levels are significantly higher than RASSF1C mRNA levels in all normal breast and lung tissues examined. In addition, RASSF1A expression is significantly downregulated in 92% of breast tumors and in 53% of lung tumors. Conversely, RASSF1C was upregulated in 62% of breast tumors and in 47% of lung tumors. Together, these findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor but instead may play a role in stimulating survival in breast and lung cancer cells.