Analysis of tumorigenesis induced by Maf oncogenes

• 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
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥47,000,000 (Direct Cost: ¥47,000,000); Fiscal Year 2009: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2008: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2007: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2006: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2005: ¥9,400,000 (Direct Cost: ¥9,400,000)
• Keywords: 転写因子 / 発がん / c-Maf / T細胞性リンパ腫 / 多発性骨髄腫 / 大Maf群転写因子 / 動物モデル / リンパ腫 / トランスジェニックマウス / c-Myc

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
  • NAID: 120007131506
  • 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
  • NAID: 10027382208
  • 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
  • NAID: 10027194339
  • Peer Reviewed
• [Journal Article] Neither MafA/L-Maf nor MafB is essential for lens development in mice (2009)
  • Author(s): Takeuchi T, et al.
  • Journal Title: Genes Cells. 14 Pages: 941-947
  • Peer Reviewed
• [Journal Article] Antitumor effects of 2-oxoglutarate through inhibition of angiogenesis in a murine tumor model (2009)
  • Author(s): Matsumoto K, et al.
  • Journal Title: Cancer Sci. 100 Pages: 1639-1647
  • Peer Reviewed
• [Journal Article] c-Maf is essential for the F4/80 expression in macrophages in vivo (2009)
  • Author(s): Nakamura M, et al.
  • Journal Title: Gene. 445 Pages: 66-72
  • Peer Reviewed
• [Journal Article] MafA-deficient and b-cell specific MafK-overexpressing hybrid transgenic mice develop human-like severe diabetic nephropathy (2009)
  • Author(s): Shimohata H, et al.
  • Journal Title: Biochem Biophys Res Commun 389 Pages: 235-240
  • Peer Reviewed
• [Journal Article] Frequent downregulation or loss of CD79a expression in plasma cell myelomas : potential clue for diagnosis (2009)
  • Author(s): Tanaka T, et al.
  • Journal Title: Pathol Int. 59 Pages: 804-808
  • Peer Reviewed
• [Journal Article] Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling (2009)
  • Author(s): Bourane S, et al.
  • Journal Title: Neuron. 64 Pages: 857-870
  • Peer Reviewed
• [Journal Article] Gene expression profile of third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development. (2009)
  • Author(s): Sultana DA, et.al
  • Journal Title: Blood (In press)
  • 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
  • NAID: 120007138832
  • Peer Reviewed
• [Journal Article] Ephrin-Al promotes the malignant progression of intestinal tumors in Apc^<min/+> mice (2008)
  • Author(s): Shi L, et.al.
  • Journal Title: Oncogene 27 Pages: 3265-3272
  • Peer Reviewed
• [Journal Article] Runxl is involved in primitive erythropoiesis in the mouse (2008)
  • Author(s): Yokomizo T, et.al.
  • Journal Title: Blood 111 Pages: 4075-4080
  • Peer Reviewed
• [Journal Article] Deletion of selertocysteine tRNA gene in macrephagce and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2. (2008)
  • Author(s): Suzuki T, et. al.
  • Journal Title: J Biol Chem. 283 Pages: 2021-2030
  • Peer Reviewed
• [Journal Article] Ephrin-Al pmotes the malignant progression of inteStinal tumors in Apc^<min/+>.mice. (2008)
  • Author(s): Shi L, et. al.
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Runxl is involved in primitive erythropoiesis in the mouse. (2008)
  • Author(s): Yokomizo T, et. al.
  • Journal Title: Blood (In press)
  • 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] c-Maf expression in angioimmunoblastic T cell lymphoma. (2007)
  • Author(s): Idate-Murakami Y, et. al.
  • Journal Title: Am J Surgical Pathol. 31 Pages: 1695-1702
  • Peer Reviewed
• [Journal Article] Suppression of MafA dependent transcription by transforming growth factor-b signaling. (2007)
  • Author(s): Matsumura H, et. al.
  • Journal Title: Biochem Biophys Res Commun. 364 Pages: 151-1561
  • Peer Reviewed
• [Journal Article] Dysfunction of Nrf2 decreases KB_rO(3)-induced oxidative DNA damage in Oggl-null mice. (2007)
  • Author(s): Jaloszynski P, et. al.
  • Journal Title: Biochem Biophys Res Commun. 364 Pages: 966-971
  • Peer Reviewed
• [Journal Article] Th1 and Type 1 cytotoxic T cells dominant responses in T-bet over-expression transgenic mice that develop allergic contact dermatitis. (2007)
  • Author(s): Ishizaki K, et al.
  • Journal Title: J Immunol. 178 Pages: 605-612
• [Journal Article] Characterization of GATA-1(+) hemangioblastic cells in the mouse embryo. (2007)
  • Author(s): Yokomizo T, et al.
  • Journal Title: EMBO J. 26 Pages: 184-196
• [Journal Article] c-Maf expression in angioimmunoblastic T cell lymphoma. (2007)
  • Author(s): Idate-Murakami Y, et al.
  • Journal Title: Am J Surgical Pathol. (in press)
• [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] MafK overexpression in pancreatic beta-cells caused impairment of glucose-stimulated insulin secretion. (2006)
  • Author(s): Shimohata H, et al.
  • Journal Title: Biochem Biophys Res Commun. 346 Pages: 671-680
• [Journal Article] MafB is essential for renal development and F4/80 expression in macrophage. (2006)
  • Author(s): Moriguchi T et al.
  • Journal Title: Mol Cell Biol. 26 Pages: 5715-5727
• [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 et al.
  • Journal Title: Blood. 108 Pages: 4018-4024
• [Journal Article] Deletion of selection cassette but not cis-acting elements in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors. (2006)
  • Author(s): Ema M, et al.
  • Journal Title: Blood 107(1) Pages: 111-117
• [Journal Article] Uterine sensitization-associated gene-1 (USAG-1), a novel BMP antagonist expressed in the kidney, accelerates tubular injury. (2006)
  • Author(s): Yanagida M, et al.
  • Journal Title: J Clin Invest. 116(1) Pages: 70-79
• [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
• [Journal Article] GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of STAT3 activity. (2005)
  • Author(s): Ezoe S, et al.
  • Journal Title: J Biol Chem. 280(13) Pages: 13163-13170
• [Journal Article] Novel Serpinopathy in Rat Kidney and Pancreas Induced by Overexpression of Megsin. (2005)
  • Author(s): Inagi R, et al.
  • Journal Title: J Am Soc Nephrol. 16(5) Pages: 1339-1349
• [Journal Article] The distal sequence element of the selenocysteine tRNA gene is a tissue dependant enhancer essential for mouse embryogenesis. (2005)
  • Author(s): Kelly VP, et al.
  • Journal Title: Mol Cell Biol. 25(9) Pages: 3658-3669
• [Journal Article] Input of Orexin/Hypocretin neurons ; revealed by a genetically encoded tracer in mice. (2005)
  • Author(s): Sakurai T, et al.
  • Journal Title: Neuron. 46(2) Pages: 297-308
• [Journal Article] MafA is a key regulator of glucose-stumulated insulin secretion. (2005)
  • Author(s): Zhang C, et al.
  • Journal Title: Mol Cell Biol. 25(12) Pages: 4969-4976
• [Journal Article] Increased dose of Runx1/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice. (2005)
  • Author(s): Yanagida M, et al.
  • Journal Title: Oncogene. 24(28) Pages: 4477-4485
• [Journal Article] GATA motifs regulate early hematopoietic lineage-specific expression of Gata2 gene. (2005)
  • Author(s): Kobayashi-Osaki M, et al.
  • Journal Title: Mol Cell Biol. 25(16) Pages: 7005-7020
• [Journal Article] Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor. (2005)
  • Author(s): Tsujino N, et al.
  • Journal Title: J Neurosci. 25(32) Pages: 7459-7469
• [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, et al.
  • Journal Title: Oncogene. 24(46) Pages: 6936-6944
• [Journal Article] Redox imbalance in cystine/glutamate transporter-deficient mice. (2005)
  • Author(s): Sato H, et al.
  • Journal Title: J Biol Chem 280(45) Pages: 37423-37429
• [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
• [Presentation] Functional analyais of large Maf transcription factors for hematopoiesis and oncogenesis. (2007)
  • Author(s): Takahashi, S.
  • Organizer: 第66回日本癌学会総会シンポジウム
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Remarks] ホームページ等
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