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Coexpression of Grb7 with Epidermal Growth Factor Receptor or Her2/erbB2 in Human Advanced Esophageal Carcinoma¹

Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874, Japan [S. T., M. M., T. A.]; Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan [K. S.]; Department of Surgery, Saitama Cancer Center, Saitama, Japan [Y. T., K. M.]; and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts [J.R.W.]

Growth factor receptors transmit intracellular signals that may be important in carcinogenesis. The Grb7 protein was recently identified as a substrate of the epidermal growth factor receptor and related Her2/erbB2 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 human Grb7 cDNA encoding for N-terminal amino acids was isolated and found to be 90% homologous to the murine counterpart. Although there was no amplification of the Grb7 gene in esophageal cancers, Grb7 mRNA was found to be overexpressed in 14 cancers (43.8%) but not in adjacent normal esophageal mucosa. It is noteworthy that coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was significantly related to extramucosal tumor invasion (P = 0.02), whereas such a relationship was not shown by each sole expression. These findings suggest a possible relationship of Grb7 signaling in association with expression of tyrosine kinase receptors in aggressive human esophageal cancer.

¹ This work was supported by a grant from the Fukuoka Cancer Society. The represented sequence has been registered with GenBank, accession no. D87513.

² To whom requests for reprints should be addressed. Phone: 81-977-24-5301, ext. 318; Fax: 81-977-24-8945.

Received 9/16/96. Accepted 11/14/96.

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