ABLATION OF G(O)-ALPHA OVERRIDES G(1) RESTRICTION POINT CONTROL THROUGH RAS ERK/CYCLIN D1-CDK ACTIVITIES/

We have generated stable IIC9 cell lines, Goa1 and Goa2, that overexpr ess full-length antisense G(o) alpha RNA, As shown previously, express ion of antisense G(o) alpha RNA ablated the a subunit of the heterotri meric G protein, G(o), resulting in growth in the absence of mitogen, To better understand this change in IIC9 phenotype, we have characteri zed the signaling pathway and cell cycle events previously shown to be important in control of IIC9 G(1)/S phase progression. In this paper we clearly demonstrate that ablation of G(o) alpha results in growth, constitutively active Ras/ERK, elevated expression of cyclin D1, and c onstitutively active cyclin D1-CDK complexes, all in the absence of mi togen, Furthermore, these characteristics were abolished by the transi ent overexpression of the transducin heterotrimeric G protein alpha su bunit strongly suggesting the transformation of G(o) alpha-ablated cel ls involves G(o) beta gamma subunits. This is the first study to impli cate a heterotrimeric G protein in tumor suppression.