Gprc5a deletion enhances the transformed phenotype in normal and malignant lung epithelial cells by eliciting persistent Stat3 signaling induced by autocrine leukemia inhibitory factor.

ABSTRACT: Signal transducers and activators of transcription 3 (Stat3) is activated by cytokines and growth factors in lung cancers and regulates expression of genes implicated in cell growth, survival, and transformation. Previously, we found that mice with a deletion of the G protein-coupled receptor, family C, group 5, member a (Gprc5a) gene develop lung tumors, indicating that Gprc5a is a tumor suppressor. Herein, we show that epithelial cells from Gprc5a knockout mouse lung (Gprc5a(-/-) cells) survive better in vitro in medium deprived of exogenous growth factors and form more colonies in semisolid medium than their counterparts from wild-type mice (Gprc5a(+/+) cells). Stat3 tyrosine 705 phosphorylation and expression of several Stat3-regulated antiapoptotic genes were higher in Gprc5a(-/-) tha

SUBMITTER: Chen Y 

PROVIDER: S-EPMC2970717 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature