V-RASH EXPRESSION CONFERS HORMONE-INDEPENDENT INVITRO GROWTH TO LNCAP PROSTATE CARCINOMA-CELLS

The LNCaP human prostate cancer cell line is dependent on androgen for in vitro growth. To discover genes that may be responsible for progression of prostate cancer from hormone dependence to hormone independence, we transfected LNCaP cells with expression vectors that contained either the v-ras(H) or c-ras(H) gene under the control of the cadmium (Cd2+)-inducible human metallothionein-IIA promoter. Numerous derivative cell lines were isolated which manifested inducible expression of ras(H) p21 protein when the cells were treated with Cd2+. None of the cell lines transfected with c-ras(H) were found to have an altered growth phenotype. Several derivative cell lines expressing inducible v-ras(H) manifested hormone-independent growth in culture when treated with 10(-7) M Cd2+.Cd2+ induction of v-ras(H) p21 was also shown to increase anchorage-independent colony formation of the v-ras(H)-expressing cell lines tested. Expression of a dominant mutated oncogene can change the hormone-dependent growth phenotype of prostate cancer cells.