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Am J Physiol Lung Cell Mol Physiol 291: L1185-L1190, 2006. First published August 4, 2006; doi:10.1152/ajplung.00072.2006
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Ras association domain family 1C protein stimulates human lung cancer cell proliferation

Yousef G. Amaar,1,3 Marlon G. Minera,1 Laurice K. Hatran,1 Donna D. Strong,2 Subburaman Mohan,2 and Mark E. Reeves1,3

1Surgical Oncology Laboratory and 2Musculoskeletal Disease Center, Loma Linda Department of Veterans Affairs Medical Center, and 3Department of Surgery, Loma Linda University, Loma Linda, California

Submitted 1 March 2006 ; accepted in final form 11 July 2006

Recently, the Ras association domain family 1 gene (RASSF1) has been identified as a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, the function of RASSF1C, both in normal and cancer cells, is still unknown. To learn more about the function of RASSF1C in human cancer cells, we tested the effect of silencing RASSF1C mRNA with small interfering RNA on lung cancer cells (NCI H1299) that express RASSF1C but not RASSF1A. Small interfering RNA specific for RASSF1C reduced RASSF1C mRNA levels compared with controls. This reduction in RASSF1C expression caused a significant decrease in lung cancer cell proliferation. Furthermore, overexpression of RASSF1C increased cell proliferation in lung cancer cells. Finally, we found that RASSF1C, unlike RASSF1A, does not upregulate N-cadherin 2 and transglutaminase 2 protein expression in NCI H1299 lung cancer cells. This suggests that RASSF1C and RASSF1A have different effector targets. Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor but rather stimulates lung cancer cell proliferation.

ribonucleic acid interference; gene expression; cell proliferation; apoptosis; cell cycle


Address for reprint requests and other correspondence: Y. G. Amaar, Loma Linda VA Medical Center, 11201 Benton St. (151), Loma Linda, CA 92357 (e-mail: yousef.amaar{at}va.gov)




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