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

Shinji Tanaka, Masaki Mori, Tsuyoshi Akiyoshi, Yoichi Tanaka, Ken Ichi Mafune, Jack R. Wands, Keizo Sugimachi

Research output: Contribution to journalArticle

63 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)821-827
Number of pages7
JournalJournal of Clinical Investigation
Volume102
Issue number4
DOIs
Publication statusPublished - Aug 15 1998

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Carcinoma
Protein Isoforms
Lymph Nodes
Antisense RNA
src Homology Domains
Epidermal Growth Factor
Base Pairing
Cell Movement
Transfection
Signal Transduction
Neoplasms
Intercellular Signaling Peptides and Proteins
Proteins
Complementary DNA
Neoplasm Metastasis
Phenotype
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Tanaka, S., Mori, M., Akiyoshi, T., Tanaka, Y., Mafune, K. I., Wands, J. R., & Sugimachi, K. (1998). A novel variant of human Grb7 is associated with invasive esophageal carcinoma. Journal of Clinical Investigation, 102(4), 821-827. https://doi.org/10.1172/JCI2921

A novel variant of human Grb7 is associated with invasive esophageal carcinoma. / Tanaka, Shinji; Mori, Masaki; Akiyoshi, Tsuyoshi; Tanaka, Yoichi; Mafune, Ken Ichi; Wands, Jack R.; Sugimachi, Keizo.

In: Journal of Clinical Investigation, Vol. 102, No. 4, 15.08.1998, p. 821-827.

Research output: Contribution to journalArticle

Tanaka, S, Mori, M, Akiyoshi, T, Tanaka, Y, Mafune, KI, Wands, JR & Sugimachi, K 1998, 'A novel variant of human Grb7 is associated with invasive esophageal carcinoma', Journal of Clinical Investigation, vol. 102, no. 4, pp. 821-827. https://doi.org/10.1172/JCI2921
Tanaka, Shinji ; Mori, Masaki ; Akiyoshi, Tsuyoshi ; Tanaka, Yoichi ; Mafune, Ken Ichi ; Wands, Jack R. ; Sugimachi, Keizo. / A novel variant of human Grb7 is associated with invasive esophageal carcinoma. In: Journal of Clinical Investigation. 1998 ; Vol. 102, No. 4. pp. 821-827.
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