2009 Fiscal Year Final Research Report
Molecular pathology for functional differentiation of human pituitary adenomas : New development of NOTCH signaling pathway.
| Project/Area Number |
19390105
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tokai University |
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Principal Investigator |
OSAMURA Yoshiyuki Tokai University, 医学部, 教授 (10100992)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEKOSHI Susumu 東海大学, 医学部, 准教授 (70216878)
UMEMURA Shinobu 東海大学, 医学部, 准教授 (20276794)
KAJIWARA Hiroshi 東海大学, 医学部, 講師 (20317754)
KIMURA Minoru 東海大学, 医学部, 教授 (10146706)
YOSHIMURA Shinichi 東海大学, 医学部, 講師 (30230808)
MATSUNO Akira 帝京大学, 医学部, 教授 (00242058)
TERAMOTO Akira 日本医科大学, 大学院・医学研究科, 教授 (60231445)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 下垂体 / Notchシグナル / 転写因子 / Wntシグナル |
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| Research Abstract |
The Notch signaling pathway is a highly conserved pathway for cell to cell interaction. It is known that this pathway is involved in the regulation of cellular differentiation and proliferation. It was reported that Notch signaling pathway functions in the pituitary gland. In mouse pituitary, persistent expression of activated Notch2 is sufficient to delay gonadotrope (LH/FSH producing cells) differentiation, and activated Notch1 suppress the corticotrope differentiation and promote the GH or TSH producing cells. The other, in human pituitary gland, it was reported that NOTCH3 mRNA was expressed in clinically nonfunctioning adenoma. However, it has not been clarified whether NOTCH signaling is related to the functions and/or growth of several adenomas. To elucidate the functional role of NOTCH signaling in human pituitary adenomas, we focused on the NOTCH3 signaling pathway in this study, and detected the expression and localization of NOTH3 receptor and NOTCH ligands DLL1, Jagged1, and Jagged2 in various types of human pituitary adenomas by immunohistochemistry. Cleaved NOTCH3 which is active form (N3ICD ; NOTCH3 intracellular domain) was localized in nuclei of pituitary adenoma cells. N3ICD was observed in all GHomas, 60% of ACTHomas, 90% of Gn-omas, and half cases of NCAs. The expression of DLL1 was detected in 90% of GHomas, 70% of ACTHomas, all cases of Gn-omas and NCAs. No signals for NOTCH3 and DLL1 were observed in TSHomas and PRLomas. These results are further suggestive of the idea that NOTCH signaling pathway plays a role in the functional differentiation of human pituitary adenomas.
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