ANALYSIS OF GENE AMPLIFICATION AND OVEREXPRESSION IN HUMAN ESOPHAGEAL-CARCINOMA CELL-LINES

Gene amplification/overexpression was analyzed in 23 cell lines derive d from human esophageal squamous-cell-carcinoma tissues by Southern an d Northern hybridizations to c-myc, c-erbB, hst-1 and cyclin-D1 probes . Amplification of the c-myc gene was observed in 5 cell lines derived from well-differentiated carcinomas and all of them were accompanied by co-amplification of other examined oncogenes. The C-erbB gene was a mplified in 3 cell lines. Co-amplification of hst-1 and cyclin D1, bot h of which are located in chromosome 11q13, was found in 9 cell lines. Without exception their amplification was simultaneous and the magnit udes were similar. Their amplification, but not their overexpression, was significantly correlated with poor prognosis in patients from whom the cell lines were established. While hst-1-gene expression was not detected, at least 1 of the genes analyzed was overexpressed in 20 cel l lines vs. its expression in normal esophageal mucosal tissues. Howev er, gene amplification was not necessarily accompanied by overexpressi on of the corresponding genes. Expression of the cyclin D1 gene, which has been assumed to be a target gene for 11q13 amplification, was not detected in one particular cell line with amplification of 11q13. The se results suggest that the amplification/overexpression of more than 1 oncogene is involved in the carcinogenic process of esophageal carci noma and that c-myc-gene amplification is associated with a well-diffe rentiated subtype. There remains a possibility that key oncogenes othe r than cyclin D1 are involved in 11q13 amplification. (C) 1994 Wiley-L iss, Inc.