Ras-Induced Phenotypic Changes in Human Fibroblasts

Abstract

DNA transfection studies have shown activated ras genes to transform established rodent cell lines in a dominant fashion and to co-operate with so-called nuclear oncogenes in primary cultures to give transformation (Land et al, 1983; Ruley, 1983; Reviewed Balmain, 1985). Activated ras genes have been identified in a wide variety of human tumour and human tumour cell line DNAs (Santos et al, 1982; Hall et al, 1983; Barbacid, 1986; Lowy and Willumsen, 1986; Bos et al, 1987) suggesting that the ras oncogene family (Ha-; Ki-; N) might have an important role to play in human tumourigenesis and human cell transformation. This is in part confirmed by the limited success of ras-induced in vitro human epithelial cell transformation (Yoakum et al, 1985; Rhim et al, 1985; Boukamp et al, 1986). However, when compared with rodent fibroblast cell transformation, very little is known about human cell transformation other than that it is very difficult to achieve either by the use of conventional carcinogenic agents (Kakunaga, 1978; Milo and DiPaolo, 1978; Milo et al, 1981) or by the introduction of activated ras genes. Several groups have reported the failure of an activated ras gene to transform normal human fibroblasts (Sager et al, 1983; Spandidos, 1985; Namba et al, 1988), whilst Sutherland et al (1985) showed pT24 Ha-ras to confer a high incidence of anchorage independence, but not tumourigenicity on neonate foreskin fibroblasts.