EXPRESSION OF GROWTH-FACTORS AND THEIR RECEPTORS IN HUMAN ESOPHAGEAL CARCINOMAS - REGULATION OF EXPRESSION BY EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-ALPHA

The expression of mRNAs for epidermal growth factor (EGF), transformin g growth factor alpha(TGFalpha), EGFR, platet-derived growth factor (P DGF) A and B chain, PDGF receptor (PDGFR), transforming growth factor beta (TGFbeta), erbB-2 and estrogen receptor (ER) genes was first exam ined in 6 human esophageal carcinoma cell lines, 6 xenoplanted and 15 surgically resected esophageal carcinomas. Secondly, the effect of EGF and TGFalpha on the expression of these genes by the TE-1 esophageal carcinoma cell line was investigated. The expression of EGF mRNA was d etected in 8 (29.6%) of 27 tumors including the cell lines, whereas th e TGFalpha and EGFR genes were expressed in 21 (77.8%) and 24 (88.9%) tumors respectively. PDGF B chain and PDGFR were detected in 18 (66.7% ) and 20 (74.1%), respectively, and ER mRNA was observed in 16 (59.3%) tumors. Genes for PDGF A chain and TGFbeta and the erbB-2 gene were c ommonly expressed. On the other hand, exogenous EGF and TGFalpha stimu lated the expressions of fos and myc genes by TE-1 cells. The expressi on of mRNAs for TGFalpha, PDGF A and B chain and the erbB-2 genes was also increased after treatment with EGF. TGFalpha increased the accumu lation of mRNAs for EGF, TGFalpha, EGFR, PDGF A and B chain and the er bB-2 gene. Moreover, the expression of mRNAs for interstitial collagen ase, stromelysin and type IV collagenase was increased after EGF or TG Falpha treatment. These results indicate that EGF and TGFalpha may reg ulate the multi-growth-factor receptor expression and may play a centr al role for tumor invasion and metastasis as autocrine modulators for human esophageal carcinoma.