title: Elevated expression of ETS-1 gene in a metastatic, tumorigenic human prostate epithelial cell line transformed by the v-Ki-ras oncogene.
abstract: A suitable in vitro model system to investigate mechanisms of human prostate carcinogenesis is much needed. We have previously demonstrated that an immortal, but non-tumorigenic, human prostate epithelial cell line (267B(1)) can be malignantly transformed by the v-Ki-ras oncogene, and it can serve as a useful model for investigation of the progression steps of prostate carcinogenesis. In this study, we report for the first time the invasive/metastatic phenotype of the v-Ki-ras transformed 267B, cells (267B(1)/Ki-ras). In addition, comparing non-tumorigenic 267B, and metastatic tumorigenic 267B(1)/Ki-ras human prostate epithelial cell lines, we have found that expression of ETS-1 and ERGB mRNA was elevated to 2-5 fold in the metastatic and tumorigenic 267B(1)/Ki-ras cell line. A specific ETS-1 monoclonal antibody E44 also revealed that the expression of ETS-1 protein level in 267B(1)/Ki-ras cell line was higher than those in 267B, cell line. However, other members of the ETS gene family such as ETS-2, GABP alpha and their mRNA expression levels were similar in both cell lines. The activation of MAP kinase, a downstream target for Ki-ras, was also shown. The expression of urokinase plasminogen activator (u-PA) was also increased in the metastatic 267B(1)/Ki-ras line. An obvious capability of invasion was observed in the 267B(1)/Ki-ras cell line, but not in the 267B(1) line using BioCoat Matrigel invasion chamber assay system. The present study has provided evidence that the v-Ki-ras oncogene may activate the nuclear target gene, ETS-1 gene, to mediate tumorigenic and metastatic capacity of the v-Ki-ras transformed prostate epithelial cells.
authors.affiliation: NCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NCI,LAB GENOM DIVERS,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC FREDERICK,FREDERICK,MD 21702.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Fisher
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Kamata
authors.forename: H
authors.initials: H
authors.lastname: Kung
authors.forename: J
authors.initials: J
authors.lastname: Lautenberger
authors.forename: J
authors.initials: J
authors.lastname: Rhim