A novel variant of human Grb7 is associated with invasive esophageal carcinoma.

Abstract	The cDNAs of a putative growth factor-bound (Grb) 7 signal transduction molecule and Grb7V novel splice variant were isolated from an invasive human esophageal carcinoma. Although both Grb7 isoforms share homology with the Mig-10 cell migration gene, the Grb7V isoform lacks 88 base pairs in the C terminus; the resultant frame shift leads to substitution of an SH2 domain with a short hydrophobic sequence. The wild-type Grb7 protein, but not the Grb7V isoform, is rapidly tyrosyl phosphorylated in response to EGF stimulation in esophageal carcinoma cells. Analysis of human esophageal tumor tissues and regional lymph nodes with metastases revealed that Grb7V was expressed in 40% of Grb7-positive esophageal carcinomas. More importantly, Grb7V expression was enhanced after metastatic spread to lymph nodes as compared to the original tumor tissues. Finally, transfection of an antisense Grb7 RNA expression construct lowered endogenous Grb7 protein levels and suppressed the invasive phenotype exhibited by esophageal carcinoma cells. These findings suggest that Grb7 isoforms are involved in cell invasion and metastatic progression of human esophageal carcinomas.
Authors	S Tanaka, M Mori, T Akiyoshi, Y Tanaka, K Mafune, J R Wands, K Sugimachi
Journal	The Journal of clinical investigation (J Clin Invest) Vol. 102 Issue 4 Pg. 821-7 (Aug 15 1998) ISSN: 0021-9738 [Print] United States
PMID	9710451 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Adaptor Proteins, Signal Transducing GRB2 Adaptor Protein GRB2 protein, human GRB7 protein, human Proteins RNA, Antisense GRB7 Adaptor Protein Tyrosine ErbB Receptors
Topics	Adaptor Proteins, Signal Transducing Alternative Splicing Amino Acid Sequence Base Sequence Carcinoma, Squamous Cell (genetics, secondary) Cell Movement ErbB Receptors (genetics) Esophageal Neoplasms (genetics, secondary) GRB2 Adaptor Protein GRB7 Adaptor Protein Humans Molecular Sequence Data Neoplasm Invasiveness Neoplasm Metastasis Phosphorylation Proteins (genetics) RNA, Antisense Sequence Homology, Amino Acid Signal Transduction Tumor Cells, Cultured (drug effects) Tyrosine (metabolism) src Homology Domains

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