Overexpression of protein tyrosine kinases in human esophageal cancer.
Using a PCR-based cloning technique, we isolated a series of protein tyrosine kinases (PTKs) expressed in a cell line of esophageal squamous cell carcinoma. Sequence analysis revealed 10 different kinds of PTKs of the receptor type [epidermal cell growth factor receptor, insulin-like growth factor I receptor, fibroblast growth factor receptor 4, eck, erk, discoidin domain receptor (DDR)/trkE/cell adhesion kinase (Cak), HEK2, HEK8, axl and sky] and one PTK of the nonreceptor type (tyk2). Subsequently, we examined the expression of the transcripts of these 11 genes in paired samples of normal and carcinomatous esophageal tissues obtained from 12 cases of esophageal cancer. We found that all 11 gene transcripts were expressed in both carcinomatous and normal tissues, and 6 of them were significantly overexpressed in carcinomatous tissues relative to adjacent normal tissues. Among these, the magnitude of mRNA expression of DDR/trkE/Cak PTK was positively correlated with the proliferative activity of carcinoma cells, but not with their degree of differentiation. Immunohistochemically, DDR was expressed in both normal and cancerous esophageal cells. The intensity of the expression was higher in cancer than normal tissue. In addition, we confirmed the expression of two isoforms of DDR/trkE/Cak in normal and cancerous esophagus. Our study suggests that DDR/trkE/Cak plays an important role in the regulation of proliferation of esophageal cancer.
Nemoto
T
T
Division of Clinical Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Japan. nemoto-path@med.tmd.ac.jp
Ohashi
K
K
Akashi
T
T
Johnson
J D
JD
Hirokawa
K
K
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D002455:Cell Division; D000070819:Discoidin Domain Receptor 1; D000070818:Discoidin Domain Receptors; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004947:Esophagus / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D036223:Receptor, EphB3; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism; D053634:TYK2 Kinase; D014407:Tumor Cells, Cultured; D000094963:Axl Receptor Tyrosine Kinase
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D011975:Receptors, Mitogen; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D000070818:Discoidin Domain Receptors; D066246:ErbB Receptors; C496371:FGFR4 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D036223:Receptor, EphB3; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017526:Receptor, IGF Type 1; C084944:TYRO3 protein, human; D053634:TYK2 Kinase; C070139:TYK2 protein, human; D020928:Mitogen-Activated Protein Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human