Malignant transformation of an epithelial cell by v-Src via tv-a-mediated retroviral infection: a new cell model for studying carcinogenesis.

Abstract

Most human cancers are of epithelial origin, but many cell culture models for the study of cancer-causing genes use fibroblasts. In addition, efficient delivery and stable expression of foreign genes into non-transformed cell lines are often difficult. To address both questions, we here established a non-transformed rat kidney epithelial RK3E cell line that constitutively expresses tv-a (receptor for subgroup A avian leukosis virus, ALV) for delivery of foreign genes via avian retroviral infection. This cell line (RK3E/tv-a) allows efficient and stable expression of either single or multiple foreign genes. Furthermore, tv-a-mediated delivery of various oncogenes (v-src, H-ras, myc or akt) leads to malignant transformation. v-src-transformed cells exhibited classical cancerous phenotypes in vitro, and induced tumor formation and lung metastasis upon injecting into immunodeficient mice. Expression profiles of downstream molecular effectors (E-cadherin, beta-catenin, cyclin D1, Myc, VEGF, MMP-2, and MMP-9) in these cells correlate with characteristics of cancerous phenotypes. This new cell model serves as a useful tool to study cancer-causing genes in epithelial cell type.