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 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.
Tanaka
S
S
Department of Surgery, Kyushu University, Beppu, Japan.
Mori
M
M
Akiyoshi
T
T
Tanaka
Y
Y
Mafune
K
K
Wands
J R
JR
Sugimachi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D066246:ErbB Receptors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051382:GRB7 Adaptor Protein; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D066246:ErbB Receptors; D051382:GRB7 Adaptor Protein; D011506:Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C495955:GRB7 protein, human; C495956:Grb7 protein, mouse