Defined genetic events associated with the spontaneous in vitro transformation of ElA/ Ras-expressing human IMR90 fibroblasts. Carcinogenesis 27: 350–359

In contrast to rodent cells, normal human fibroblasts are generally resistant to neoplastic transformation in vitro. Here, we report the derivation and characterization of a spontaneously transformed cell line from normal human IMR90 fibroblasts transduced with E1A and Ras onco-genes. Unlike the parental, non-tumorigenic E1A/Ras-expressing IMR90 cells, these spontaneously transformed cells displayed aberrant growth potential in vitro and were capable of tumorigenesis in vivo. In contrast to the parental E1A/Ras-expressing cells, both the spontaneously trans-formed cells and cells derived from resultant tumors displayed specific t(7q;8q) and t(5q;17) structural chromo-somal changes. Chromosome 8q contains c-Myc, which is capable of activating the telomerase catalytic subunit hTERT. Notably, upregulation of c-Myc, hTERT an