In human lung epithelial cancer cell line H460, an accumulation of epidermal growth factor receptors (EGF-R) was observed following treatment with 1 μM retinoic acid. An increase in125I-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.
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