Neoplastic transformation of rat colon epithelial cells by expression of activated human K-ras.

Abstract

Somatic mutations of the K‐ras oncogene play an important role in colorectal carcinogenesis. We determined whether rat colon epithelial cells could be transformed by introducing retroviruses carrying the activated human K‐ras oncogene alone. Primary epithelial cells from the rat distal colon were infected with retroviruses carrying wild‐type and two types of activated K‐ras (asp and val at codon 12) cDNAs. Cells infected with the wild‐type K‐ras virus showed no change in morphology and died within 3 weeks, whereas the activated K‐ras virus‐infected cells underwent morphological changes within 3 days and continued to proliferate. From these cells, several cell lines were subsequently established. Epithelial cells transformed by activated K‐ras formed colonies in soft agar culture and tumors in athymic nude mice. Multiple copies of human K‐ras genes and large amounts of K‐ras mRNAs and proteins were found in the transformed cells. These data suggest that overexpression of activated K‐ras transforms rat colon epithelial cells.