1997 Fiscal Year Final Research Report Summary
Basic research and clinical application of SAP-1, a protein tyrosine phosphatase expressed in gastrointestinal cancers.
| Project/Area Number |
08557041
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Gastroenterology
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| Research Institution | Kobe University |
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Principal Investigator |
MATOZAKI Takashi Kobe University, School of Medicine, Assistant professor, 医学部・附属病院, 助手 (80252782)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Motoo Novaltis Pharma, Chief, 宝塚研究所, 部長
KITAGAWA Motoji Nagoya University, School of Medicien, Assistant Professor, 医学部・附属病院, 助手 (80262898)
TAKEYAMA Yoshifumi Kobe University, School of Medicine, Assistant Professor, 医学部, 助手 (70263374)
HAYASHI Yoshitaka Kobe University, School of Medicine, Assocaite Professor, 医学部, 助教授 (50189669)
AOYAMA Nobuo Kobe University, School of Medicine, Assistant Professor, 医学部, 助手 (30243299)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Protein tyrosine phosphatse / SAP-1 / Gastrointestinal cancer / Antibody / Inhibitor |
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| Research Abstract |
Since the level of tyrosine phosphorylation is determined by the balance between the actions of both protein tyrosine kinases and protein tyrosine phosphatases (PTPases), not only the unregulated activation of PTKs but also the inactivation of PTPases may be involved in the malignant transformation of gastrointestinal cells. SAP-1 is a human transmembrane-type PTPase that has recently been molecularly cloned. This enzyme contains a single PTPase domain in the cytoplasmic region and eight fibronectin type III-like domains with multiple potential N-glycosylation sites in the extracellular region. SAP-1 is abundant in human colorectal cancer cell lines and pancreatic cancer cell lines but not in the corresponding normal tissues. In this study, we investigated the physiological roles of SAP-1 and clinical applications of SAP-1. (1) Overexpression of SAP-1 inhibited growth of cultured cells. SAP-1 binds to EGF receptors. (2) Genomic DNA of SAP-1 promoter region was cloned and several transcription factor binding elements were observed. (3) With the use of immunohistochemistry, we have now examined the expression of SAP-1 in surgically or endoscopically excised colorectal cancers, adenoma and normal colon mucosa. Normal colon tissue or adenomas with mild dysplasia showed no detectable expression of SAP-1. In contrast, 19 of 48 (40%) adenocarcinomas expressed SAP-1. Sequencing of the K-RAS gene revealed that 10 of 15 (67%) SAP-1-positive cancers contained a mutation in codon 12. These results suggest that SAP-1 is frequently overexpressed in human colorectal cancers and that such overexpression may occur relatively late in the adenoma-carcinoma sequence. We will further investigate the existance of soluble form of SAP-1 in serm of patients with cob-rectal or pancreatic cancers.
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