American Association for Cancer Research
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Supplementary Figure Legends 1-2 from Protein Kinase C δ Is a Downstream Effector of Oncogenic K-ras in Lung Tumors

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journal contribution
posted on 2023-03-30, 20:25 authored by Jennifer M. Symonds, Angela M. Ohm, Cristan J. Carter, Lynn E. Heasley, Theresa A. Boyle, Wilbur A. Franklin, Mary E. Reyland
Supplementary Figure Legends 1-2 from Protein Kinase C δ Is a Downstream Effector of Oncogenic K-ras in Lung Tumors



Oncogenic activation of K-ras occurs commonly in non–small cell lung cancer (NSCLC), but strategies to therapeutically target this pathway have been challenging to develop. Information about downstream effectors of K-ras remains incomplete, and tractable targets are yet to be defined. In this study, we investigated the role of protein kinase C δ (PKCδ) in K-ras–dependent lung tumorigenesis by using a mouse carcinogen model and human NSCLC cells. The incidence of urethane-induced lung tumors was decreased by 69% in PKCδ-deficient knockout (δKO) mice compared with wild-type (δWT) mice. δKO tumors are smaller and showed reduced proliferation. DNA sequencing indicated that all δWT tumors had activating mutations in KRAS, whereas only 69% of δKO tumors did, suggesting that PKCδ acts as a tumor promoter downstream of oncogenic K-ras while acting as a tumor suppressor in other oncogenic contexts. Similar results were obtained in a panel of NSCLC cell lines with oncogenic K-ras but which differ in their dependence on K-ras for survival. RNA interference–mediated attenuation of PKCδ inhibited anchorage-independent growth, invasion, migration, and tumorigenesis in K-ras–dependent cells. These effects were associated with suppression of mitogen-activated protein kinase pathway activation. In contrast, PKCδ attenuation enhanced anchorage-independent growth, invasion, and migration in NSCLC cells that were either K-ras–independent or that had WT KRAS. Unexpectedly, our studies indicate that the function of PKCδ in tumor cells depends on a specific oncogenic context, as loss of PKCδ in NSCLC cells suppressed transformed growth only in cells dependent on oncogenic K-ras for proliferation and survival. Cancer Res; 71(6); 2087–97. ©2011 AACR.