Analysis of tumorigenesis induced by Maf oncogenes

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013016
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: TAKAHASHI Satoru University of Tsukuba, 大学院・人間総合科学研究科, 教授 (50271896)
• Project Period (FY): 2005 – 2009
• Keywords: 転写因子 / 発がん / c-Maf / T細胞性リンパ腫 / 多発性骨髄腫

Research Abstract

To elucidate in vivo function of Maf oncogenes for tumorigenesis, I tried to generate transgenic mice which overexpressed c-Maf in lymphoid cells. By analyzing these mice, I identified the development of lymphomas. ARK5, Cyclin D2 and Integrinβ7 were confirmed as target genes of c-Maf in the tumor cells. In addition, I analyzed patients with T cell lymphomas and found that c-Maf was overexpressed in Anigioimmunoblastic T cell lumphoma (AILT) cells in collaboration. These results indicate that c-Maf is the responsible gene for tumorigenesis of lymphocytes.

Research Products

• [Journal Article] Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development. (2009)
  • Author(s): Sultana DA, Tomita S, Hamada M, Iwanaga Y, Kitahama Y, Khang NV, Hirai S, Ohigashi I, Nitta S, Amagai T, Takahashi S, Takahama Y.
  • Journal Title: Blood. 113 Pages: 2976-2987
  • Peer Reviewed
• [Journal Article] c-Maf is essential for the F4/80 expression in macrophages in vivo. (2009)
  • Author(s): Nakamura M, Hamada M, Hasegawa K, Kusakabe M, Suzuki H, Greaves DR, Moriguchi T, Kudo T, Takahashi S.
  • Journal Title: Gene 445 Pages: 66-72
  • Peer Reviewed
• [Journal Article] Frequent downregulation or loss of CD79a expression in plasma cell myelomas: potential clue for diagnosis. (2009)
  • Author(s): Tanaka T, Ichimura K, Sato Y, Takata K, Morito T, Tamura M, Kondo E, Ohara N, Yanai H, Sasaki M, Takahashi S, Yoshino T.
  • Journal Title: Pathol Int. 59 Pages: 804-808
  • Peer Reviewed
• [Journal Article] Antitumor effects of 2-oxoglutarate through inhibition of angiogenesis in a murine tumor model. (2009)
  • Author(s): Matsumoto K, Obara N, Ema M, Horie M, Naka A, Takahashi S, Imagawa S.
  • Journal Title: Cancer Sci. 100 Pages: 1639-1647
  • Peer Reviewed
• [Journal Article] Ephrin-A1 promotes the malignant progression of intestinal tumors in Apcmin/+ mice. (2008)
  • Author(s): Shi L, Itoh F, Itoh S, Takahashi S, Yamamoto M, Kato M.
  • Journal Title: Oncogene 27 Pages: 3265-3272
  • Peer Reviewed
• [Journal Article] Runx1 is involved in primitive erythropoiesis in the mouse. (2008)
  • Author(s): Yokomizo T, Hasegawa K, Ishitobi H, Ema M, Osato M, Ito Y, Yamamoto M, Takahashi S.
  • Journal Title: Blood 111 Pages: 4075-4080
  • Peer Reviewed
• [Journal Article] c-Maf expression in angioimmunoblastic T cell lymphoma. (2007)
  • Author(s): Idate-Murakami Y, Yatabe Y, Sakaguchi T, Sasaki E, Yamashita Y, Morito N, Yoh Y, Fujioka Y, Matsuno F, Hata H, Mitsuya H, Imagawa S, Suzuki A, Esumi H, Sakai M, Takahashi S, Mori N.
  • Journal Title: Am J Surgical Pathol. 31 Pages: 1695-1702
  • Peer Reviewed
• [Journal Article] Characterization of GATA-1(+) hemangioblastic cells in the mouse embryo. (2007)
  • Author(s): Yokomizo T, Takahashi S, Mochizuki N, Kuroha T, Ema M, Wakamatsu A, Shimizu R, Ohneda O, Osato M, Okada H, Komori T, Ogawa M, Nishikawa S, Ito Y, Yamamoto M.
  • Journal Title: EMBO J. 26 Pages: 184-196
  • Peer Reviewed
• [Journal Article] Suppression of MafA dependent transcription by transforming growth factor-βsignaling. (2007)
  • Author(s): Matsumura H Kudo K, Harada A, Esaki R, Suzuki H, Kato M, Takahashi S.
  • Journal Title: Biochem Biophys Res Commun. 364 Pages: 151-156
  • Peer Reviewed
• [Journal Article] Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human. (2006)
  • Author(s): Morito N, Yoh K, Fujioka Y, Nakano T, Shimohata H, Yamada A, Maeda A, Matsuno F, Hata H, Suzuki A, Imagawa S, Mitsuya H, Esumi H, Koyama A, Yamamoto M, Mori N, Takahashi S.
  • Journal Title: Cancer Res. 66 Pages: 812-819
  • Peer Reviewed
• [Journal Article] MafB is essential for renal development and F4/80 expression in macrophage. (2006)
  • Author(s): Moriguchi T, Hamada M, Morito N, Terunuma T, Hasegawa K, Zhang C, Yokomizo T, Esaki R, Kuroda E, Yoh K, Kudo T, Nagata M, Greaves DR, Engel JD, Yamamoto M, Takahashi S.
  • Journal Title: Mol Cell Biol. 26 Pages: 5715-5727
  • Peer Reviewed
• [Journal Article] Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin and CD34 in the mouse embryo. (2006)
  • Author(s): Ema M, Yokomizo T, Wakamatsu A, Terunuma T, Yamamoto M, Takahashi S.
  • Journal Title: Blood. 108 Pages: 4018-4024
  • Peer Reviewed
• [Journal Article] Increased dose of Runx1/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice. (2005)
  • Author(s): Yanagida M, Osato M, Yamashita N, Liqun H, Jacob B, Wu F, Cao X, Nakamura T, Yokomizo T, Takahashi S, Yamamoto M, Shigesada K, Ito Y.
  • Journal Title: Oncogene 24 Pages: 4477-4485
  • Peer Reviewed
• [Journal Article] ARK5 is transcriptionally regulated by large Maf family to mediate IGF-1-induced cell invasion in multiple myeloma. (2005)
  • Author(s): Suzuki A, Iida S, Kato-Uranishi M, Tajima E, Zhan F, Hanamura I, Huang Y, Ogura T, Takahashi S, Ueda R, Esumi H.
  • Journal Title: Oncogene. 24 Pages: 6936-6944
  • Peer Reviewed
• [Journal Article] MafA is a key regulator of glucose-stumulated insulin secretion. (2005)
  • Author(s): Zhang C, Moriguchi T, Kajihara M, Esaki R, Harada A, Shimohata H, Oishi H, Hamada M, Morito N, Hasegawa H, Kudo T, Engel JD, Yamamoto M, Takahashi S.
  • Journal Title: Mol Cell Biol. 25 Pages: 4969-4976
  • Peer Reviewed
• [Presentation] Functional analysis of large Maf transcription factors for hematopoiesis and oncogenesis. (2007)
  • Author(s): akahashi S.
  • Organizer: 第66回日本癌学会総会シンポジウム2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Remarks] ホームページ等
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html