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), transforming growth factor alpha(TGFalpha), EGFR, platet-derived growth factor (PDGF) A and B chain, PDGF receptor (PDGFR), transforming growth factor beta (TGFbeta), erbB-2 and estrogen receptor (ER) genes was first examined 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 detected in 8 (29.6%) of 27 tumors including the cell lines, whereas the 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 commonly expressed. On the other hand, exogenous EGF and TGFalpha stimulated the expressions of fos and myc genes by TE-1 cells. The expression of mRNAs for TGFalpha, PDGF A and B chain and the erbB-2 genes was also increased after treatment with EGF. TGFalpha increased the accumulation of mRNAs for EGF, TGFalpha, EGFR, PDGF A and B chain and the erbB-2 gene. Moreover, the expression of mRNAs for interstitial collagenase, stromelysin and type IV collagenase was increased after EGF or TGFalpha treatment. These results indicate that EGF and TGFalpha may regulate the multi-growth-factor receptor expression and may play a central role for tumor invasion and metastasis as autocrine modulators for human esophageal carcinoma.