Treatment of v-Ki-Ras-transformed SVC1 cells with low retinoic acid induces malignancy reversion associated with Ras p21 down-regulation

The effect of nontoxic, low concentrations (10(-8) M) of retinoic acid (RA) for a relatively long time (28 days) on a Kirsten ras-virus transformed ce ll line (Ki-SVC1), derived from the rat seminal vesicle epithelium, was inv estigated. In these experimental conditions, the cell treatment with RA ind uced a decrease of the proliferation rate, apoptosis and a marked reduction of both anchorage-independent growth and tumorigenicity. These biological responses were either preceded or associated with important changes in aden ylate cyclase/protein kinase C signaling pathways, the activation of import ant apoptosis-linked genes and a marked decrease of the v-Ki-ras p21 protei n. The significance of these findings is discussed. (C) 2000 Elsevier Scien ce B.V. All rights reserved.