Retinoic Acid Modulates Epidermal Growth Factor Receptor Expression in Human Lung Epithelial Cancer Cells.

Abstract

In human lung epithelial cancer cell line H460, an accumulation of epidermal growth factor receptors (EGF-R) was observed following treatment with 1 &mgr;M retinoic acid. An increae in (125)I-labeled EGF binding capacity was detected, which reached its highest level after 48 h of incubation with retinoic acid. Transiently increased autophosphorylation of EGF-R after 48 h of retinoic acid treatment correlated with enhancement of EGF binding capacity on the H460 cell surface. Nuclear run-on analysis indicated that retinoic acid upregulates transcription of the EGF-R gene, reaching a maximum at 48 h and decreasing after 72 h of treatment. When retinoic acid-treated cells were chased in drug-free medium, the increased EGF-R transcript level remained unchanged. Up-regulated expression of EGF-R in H460 cells is reflected by their increasing tumorigenicity phenotype. The results demonstrate that retinoic acid induces EGF-R synthesis in human lung cancer cells. Copyright 1995 S. Karger AG, Basel