Increased Susceptibility of ras-Transformed Cells To Phenylacetate is Associatedwith Inhibition of p21ras Isoprenylation and Phenotypic Reversion

摘要

Alterations in the expression of ras oncogenes are characteristic of a widevariety of human neoplasms. Accumulating evidence has linked elevated ras expression with disease progression and with failure of tumors to respond to conventional therapies, including radiotherapy and certain chemotherapies. These observations led us to investigate the response of ras-transformed cells to the differentiation-inducer phenylacetate (PA). Using gene transfer models, we show that PA caused cytostasis in ros-transformed mesenchymal cells, associated with increased expression of 2', 5'-oligoadenylate synthetase, an enzyme implicated in negative growth control. PA also induced phenotypic reversion characterized by loss of anchorage. independent growth, reduced invasiveness and increased expression of collagen a type I, a marker of cell differentiation. The anti-tumor