Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers.
Crk is a signaling adaptor protein which is mostly composed of SH2 and SH3 domains, and has been shown to play a pivotal role in cell proliferation, differentiation, and migration. Because Crk was originally isolated as an avian sarcoma virus CT10 encoding oncoprotein v-Crk, we examined a potential role for c-Crk in the carcinogenesis of human cancers. First, to analyze gene mutations of c-Crk, we isolated a human bacterial artificial chromosome clone containing Crk genome and exon/intron structures. However, polymerase chain reaction-single strand conformation polymorphism methods failed to show any genomic mutations in the Crk exon which could be related to carcinogenesis. Second, immunohistochemical analysis of c-Crk-II demonstrated that the levels of c-Crk-II were significantly elevated in most of the tumors, particularly in the colon and lung cancers. Furthermore, immunoblot analysis using human lung cancer cell lines revealed that the expression levels of c-Crk-II were correlated to growth rates of cells. The elevated expression levels of c-Crk-II might be related to the development of human cancers.
Nishihara
Hiroshi
H
Laboratory of Molecular and Cellular Pathology, Hokkaido University School of Medicine, N 15, W7, Kita-ku, Sapporo, Japan.
Tanaka
Shinya
S
Tsuda
Masumi
M
Oikawa
Sumie
S
Maeda
Masae
M
Shimizu
Michio
M
Shinomiya
Hiroichi
H
Tanigami
Akira
A
Sawa
Hirofumi
H
Nagashima
Kazuo
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D050736:Oncogene Protein v-crk; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011494:Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors; D018909:src Homology Domains
D050736:Oncogene Protein v-crk; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D015682:Retroviridae Proteins, Oncogenic; D011494:Protein Kinases