COEXPRESSION OF GRB7 WITH EPIDERMAL GROWTH-FACTOR RECEPTOR OR HER2 ERBB2 IN HUMAN ADVANCED ESOPHAGEAL-CARCINOMA/

Growth factor receptors transmit intracellular signals that may be imp ortant in carcinogenesis. The Grb7 protein was recently identified as a substrate of the epidermal growth factor receptor and related Her2/e rbB2 receptor-linked tyrosine kinase activity. The Grb7 gene has been found to be coamplified with Her2/erbB2 in breast carcinomas. In this study, Grb7 expression was studied in 32 human esophageal cancers. A h uman Grb7 cDNA encoding for N-terminal amino acids was isolated and fo und to be 90% homologous to the murine counterpart. Although there was no amplification of the Grb7 gene in esophageal cancers, Grb7 mRNA wa s found to be overexpressed in 14 cancers (43.8%) but not in adjacent normal esophageal mucosa. It is noteworthy that coexpression of Grb7 w ith epidermal growth factor receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was significantly related to extramu cosal tumor invasion (P = 0.02), whereas such a relationship was not s hown by each sole expression. These findings suggest a possible relati onship of Grb7 signaling in association with expression of tyrosine ki nase receptors in aggressive human esophageal cancer.