Reduced receptor expression for platelet-derived growth factor and epidermal growth factor in dividing mouse lung epithelial cells

The roles of growth factors in mouse lung neoplasia were investigated by ex amining receptors for platelet-derived growth factor (PDGF) and epidermal g rowth factor (EGF) in epithelial cell lines. Whereas nontumorigenic lung ce lls expressed mRNA and protein for PDGF receptor (PDGFR)-alpha, PDGFR-beta, and EGF receptor (EGFR), five of six neoplastic lines did not. Because thi s exceptional tumorigenic cell line grows slowly, we hypothesized that rece ptor levels increased with cell stasis. To test this hypothesis, serum conc entrations were manipulated, and log-phase and postconfluent cells were com pared. Consistent with our hypothesis, PDGFR-alpha and EGFR contents, but n ot PDGFR-beta contents, increased at stasis. Ki-ras mutation initiates lung tumorigenesis in mice, but activation of Ki-ras did not affect receptor ex pression. This was determined both by transfecting nontumorigenic cells wit h activated Ki-ras and neoplastic cells with a Ki-ras antisense construct a nd by diminishing Ki-ras activation by using a farnesyltransferase inhibito r. Stasis-associated upregulation of growth-factor receptor expression sugg ests a function in lung cell differentiation that is abrogated during neopl astic growth. (C) 1999 Wiley-Liss, Inc.