An epitope localized in c-Src negative regulatory domain is a potential marker in early stage of colonic neoplasms.
In previous work, we established a new monoclonal antibody that specifically recognizes the active form of c-Src tyrosine kinase (Kawakatsu et al, 1996). To determine whether c-Src is active in colorectal tumorigenesis, we examined the expression of an active form of c-Src in human normal mucosa, hyperplastic polyps, adenomas, and adenocarcinomas. The tissue distribution of the active form of c-Src was studied by immunohistochemistry using this antibody, termed Clone 28. Among 66 cases of adenoma tested, 61 (92%) showed positive staining (adenoma with mild atypia, 3 of 3; adenoma with moderate atypia, 38 of 42; adenoma with severe atypia, 20 of 21). In contrast to the frequent and intense staining in adenomas, adenocarcinoma showed weak staining with less frequency in 4 of 16 (25%) cases. The number of specimens with positive staining in well- and moderately differentiated adenocarcinomas was limited to an early stage. The active form of c-Src mainly localized to the nuclear membrane and the perinuclear region. These results provide the first direct evidence that the activation of c-Src appears to be an early event in colonic carcinogenesis in situ. The findings of the present study thus allow us to propose a molecular mechanism involving c-Src activation in the process of malignant transformation of the human colonic neoplastic cells.
Sakai
T
T
Division of Hemopoiesis, Institute of Hematology, Jichi Medical School, Tochigi, Japan.
Kawakatsu
H
H
Fujita
M
M
Yano
J
J
Owada
M K
MK
D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor; D000081247:CSK Tyrosine-Protein Kinase; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D000939:Epitopes / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D016391:Genes, src / Q000235:genetics*; D006801:Humans; D009367:Neoplasm Staging; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000939:Epitopes; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human