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

The roles of growth factors in mouse lung neoplasia were investigated by examining receptors for platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) in epithelial cell lines. Whereas nontumorigenic lung cells expressed mRNA and protein for PDGF receptor (PDGFR)-alpha, PDGFR-beta, and EGF receptor (EGFR), five of six neoplastic lines did not. Because this exceptional tumorigenic cell line grows slowly, we hypothesized that receptor levels increased with cell stasis. To test this hypothesis, serum concentrations were manipulated, and log-phase and post-confluent cells were compared. Consistent with our hypothesis, PDGFR-alpha and EGFR contents, but not PDGFR-beta contents, increased at stasis. Ki-ras mutation initiates lung tumorigenesis in mice, but activation of Ki-ras did not affect receptor expression. This was determined both by transfecting nontumorigenic cells with activated Ki-ras and neoplastic cells with a Ki-ras antisense construct and by diminishing Ki-ras activation by using a farnesyltransferase inhibitor. Stasis-associated upregulation of growth-factor receptor expression suggests a function in lung cell differentiation that is abrogated during neoplastic growth.