2013 Fiscal Year Final Research Report
Repression of the Akt pathway by a novel tumor suppressor gene PHLDA3 -towards development of tailor-made therapies-
| Project/Area Number |
23501279
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
OHKI Rieko 独立行政法人国立がん研究センター, 研究所, 主任研究員 (70356252)
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| Project Period (FY) |
2011 – 2013
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| Keywords | p53 / Akt |
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| Research Abstract |
Pancreatic neuroendocrine tumors (PanNETs) are a rare pathology and molecular mechanisms underlying their development have not been well defined. We showed that a 2-hit inactivation of the PHLDA3 gene is required for PanNET development: methylation of the locus and loss of heterozygosity. PHLDA3 functions as a suppressor of PanNETs via repression of Akt activity and downstream Akt-regulated biological processes. In addition, the tumor-suppressing pathway mediated by MEN1, a well-known suppressor of PanNETs, is dependent on the pathway mediated by PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET development. Novel PHLDA3-mediated pathway of tumor suppression that is important in the development of PanNETs is demonstrated, and the findings may contribute to personalized medicine of PanNET patients.
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[Journal Article] PHLDA3 is a novel tumor suppressor of neuroendocrine tumors2014
Author(s)
Rieko Ohki, Kozue Saito, Yu Chen, Tatsuya Kawase, Yukie Aita, Nobuyoshi Hiraoka, Raira Saigawa, Maiko Minegishi, Goichi Yanai, Hiroko Shimizu, Shinichi Yachida, Naoaki Sakata, Akihiko Yokoyama, Ryuichiro Doi, Tomoo Kosuge, Kazuaki Shimada, Benjamin Tycko, Toshihiko Tsukada, Yae Kanai, Shoichiro Sumi, Hideo Namiki, Yoichi Taya, Tatsuhiro Shibata and Hitoshi Nakagama
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Journal Title
PNAS
Volume: 111(23)
Pages: E2404-E2413
Peer Reviewed
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[Journal Article] Cancer susceptibility polymorphism of p53 at codon 72 affects phosphorylation and degradation of p53 protein2011
Author(s)
Chikako Ozeki, Tatsuhiro Shibata, Takashi Kohno, Yuichiro Sawai, Koji Okamoto, Jun Yokota, Fumio Tashiro, Seiichi Tanuma, Ryuichi Sakai, Tatsuya Kawase, Issay Kitabayashi, Yoichi Taya and Rieko Ohki#
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Journal Title
Journal of Biological Chemistry
Volume: Vol.286
Pages: 18251-18260
Peer Reviewed
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