Advances in Bioscience and Biotechnology, 2014, 5, 73-80 ABB http://dx.doi.org/10.4236/abb.2014.51011 Published Online January 2014 (http://www.scirp.org/journal/abb/ ) OPEN ACCESS Cell-type specific and non-redundant anti-proliferative effects of shRNA-mediated Galpha12- and Galpha13 knockdown in lung cancer cell lines Thomas R. H. Büch 1,2*# , Marius Grzelinski 1,2,3# , Olaf Pinkenburg 1,2,4 , Thomas Gudermann 5,6 , Achim Aigner 1,2* 1 Rudolf-Boehm-Institute for Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany 2 Biochemical Pharmacological Institute/bpc, Philipps-University Marburg, Marburg, Germany 3 Present Address: Targos Molecular Pathology GmbH, Kassel, Germany 4 Present Address: Institute for Immunology, Philipps-University Marburg, Marburg, Germany 5 Walther Straub Institute of Pharmacology and Toxicology, University of Munich (LMU), Munich, Germany 6 Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research, Munich, Germany Email: * achim.aigner@medizin.uni-leipzig.de Received 13 November 2013; revised 24 December 2013; accepted 13 January 2014 Copyright © 2014 Thomas R. H. Büch et al. This is an open access article distributed under the Creative Commons Attribution Li- cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In accordance of the Creative Commons Attribution License all Copyrights © 2014 are reserved for SCIRP and the owner of the intel- lectual property Thomas R. H. Büch et al. All Copyright © 2014 are guarded by law and by SCIRP as a guardian. ABSTRACT In small cell lung cancer cells, various autocrine sti- muli lead to the parallel activation of Gq/11 and G 12/13 proteins. The contribution of the Gq/11-PLC-β cas- cade to the mitogenic effects in SCLC cells is well es- tablished, but the relevance of G 12/13 signaling is less explored. While in prostate and breast cancer, G 12/13 activation has been shown previously to promote in- vasiveness without being involved in cellular prolife- ration, previous data from our group indicate anti- proliferative effects of G 12/13 knockdown in small cell lung cancer (SCLC) cells. To further investigate the role of G 12/13 -dependent signaling in lung tumor cells, we employed shRNA-mediated targeting of Gα 12 , Gα 13 , or both, in SCLC and NSCLC cell lines. Lenti- viral expression of shRNAs resulted in specific Gα 12 and Gα 13 knockdown. Of note, upon single knock- down of one family member, no counter-upregulation of the other one was observed. Interestingly, inhibi- tion of proliferation was cell line dependent. In cell lines where knock-down led to antiproliferation, sin- gle knockdown of either Gα 12 or Gα 13 was sufficient to impair proliferation and double knockdown of Gα 12 and Gα 13 tended not to further increase an- ti-proliferative effects. Likewise, when single knock- down was insufficient for an inhibition of prolifera- tion, no effects were observed in double knockdowns. Taken together, these findings indicate that both Gα 12 and Gα 13 affect cellular proliferation individually and interference with one family member is sufficient for anti-tumor effects. KEYWORDS Galpha12; Galpha13; G 12/13 ; Lung Cancer; SCLC; NSCLC; Gene Knockdown 1. INTRODUCTION Lung cancer represents the leading cause of cancer-re- lated death in the industrialized countries. Cancers of the lung are subdivided into different histological subtypes, e.g., adenocarcinoma, squamous cell carcinoma, large cell carcinoma and small cell carcinoma (SCLC). The former three subtypes are often subsumed as non-small cell carcinoma (NSCLC). Lung cancer of the SCLC type shows a very aggressive behavior with early manifesta- tion of metastases. Thus, local therapeutic options like surgery are usually inapplicable in this tumor entity at the time of diagnosis. While current chemotherapy regi- mens in SCLC tumors clearly show clinical benefit, the overall survival after 5 years is still only 7% - 12% [1]. In NSCLC, although the potential to develop metastases is generally somewhat lower as compared to SCLC, dis- semination is frequent at the time of diagnosis, necessi- tating systemic chemotherapy. This clearly emphasizes the need for novel treatment strategies based on the de- * Corresponding author. # These authors contributed equally to the work.