v-rasH expression confers hormone-independent in vitro 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-rasH or c-rasH gene under the control of the cadmium (Cd2+)-inducible human metallothionein-IIA promoter. Numerous derivative cell lines were isolated which manifested inducible expression of rasH p21 protein when the cells were treated with Cd2+. None of the cell lines transfected with c-rasH were found to have an altered growth phenotype. Several derivative cell lines expressing inducible v-rasH manifested hormone-independent growth in culture when treated with 10(-7) M Cd2+ . Cd2+ induction of v-rasH p21 was also shown to increase anchorage-independent colony formation of the v-rasH-expressing cell lines tested. Expression of a dominant mutated oncogene can change the hormone-dependent growth phenotype of prostate cancer cells.
Voeller
H J
HJ
Division of Medical Oncology, Lombardi Cancer Research Center, Georgetown University, Washington, D.C. 20007.
Wilding
G
G
Gelmann
E P
EP
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002455:Cell Division; D013196:Dihydrotestosterone / Q000494:pharmacology; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D002104:Cadmium; D013196:Dihydrotestosterone; D008668:Metallothionein; D015689:Oncogene Protein p21(ras)