Neoplastic transformation of rat colon epithelial cells by expression of activated human K-ras.
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.
Investigative Treatment Division, National Cancer Center Research Institute East, Kashiwa, Chiba.
K
K
Sugiyama
K
K
Otori
H
H
Esumi
D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003110:Colonic Neoplasms / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D011905:Genes, ras; D006801:Humans; D007633:Keratins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D018631:ras Proteins / Q000032:analysis
D012333:RNA, Messenger; D007633:Keratins; D018631:ras Proteins