Plasmid-aided insertion of MMTV-LTR and ras DNAs to NIH 3T3 fibroblast cells makes them responsive to 2,3,7,8-TCDD causing overexpression of p21ras and down-regulation of EGF receptor.

Abstract

TCDD administered to NIH 3T3 fibroblast cells transfected with a plasmid containing MMTV-LTR and mouse ras DNAs caused an increased level of p21ras protein and down-regulation of EGF receptor. This effect occurred only in the cells with introduced N-ras or Ha-ras under transcriptional control of glucocorticoid-sensitive MMTV-LTR but not ones without these DNAs. The MMTV-LTR ras-incorporated cells treated with either dexamethasone or TCDD grew in soft agar to form colonies (anchorage independent growth), while nontreated cells did not, indicating profound cellular changes due to activation of N-ras by these two agents.