Role of the AIP gene in tumorigenesis of growth hormone-producing cells

• Project/Area Number: 19591079
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokushima
• Principal Investigator: YOSHIMOTO Katsuhiko The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 教授 (90201863)
• Co-Investigator(Kenkyū-buntansha): IWATA Takeo 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (10350399) ; MIZUSAWA Noriko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80254746)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 癌 / 内分泌腺 / 下垂体 / 家族性腫瘍 / 内分泌 / 遺伝学

Research Abstract

我が国における家族性成長ホルモン(GH)産生腺腫家系における遺伝子解析
巨人症を示した2人の兄弟とその叔父の3名のGH産生腺腫を示すA家系において、第11染色体長腕13.3領域に位置するAIP遺伝子にc.286-287delGTの胚細胞変異を認めた。本変異の結果、短縮型AIP蛋白が生成されることとなる。しかもGH産生腺腫それぞれにAIP遺伝子座位に正常対立遺伝子の消失(LOH)を認めた。
孤発性GH産生腺腫の解析
家族性発症が認められない40例のGH産生腺腫において、1例にAIP遺伝子c.145G>A(バリンからメチオニンへの変化)を検出した。発症への関与については今後の検討が必要である。
AIP過剰発現による細胞増殖抑制
EK293, GH3, TIG3細胞に野生型AIPを発現させると細胞増殖抑制が認められた。変異型では、その作用を有していなかった。
正常下垂体および下垂体腺腫におけるAIP蛋白の発現解析
正常下垂体ではAIP蛋白はGHとプロラクチン細胞に局在し、分泌顆粒に存在すること、孤発性下垂体腺腫においては、全てのサブタイプに発現していることを認めた。

Research Products

• [Journal Article] 副甲状腺機能亢進症-顎腫瘍症候群の原因遺伝子産物パラフィプロミン (2009)
  • Author(s): 岩田武男
  • Journal Title: 四国歯学会雑誌 21 Pages: 327-332
• [Journal Article] Identification of cis-acting promoter sequences required for expression of the glycerol-3-phosphate acyltransferase 1 gene in mice (2009)
  • Author(s): Nakagasva T, Yin Y, Hattori A, Zenitani T, Hara S, Yonemoto H, Nakamura A, Nakano M, Mawatari K, Teshigawara K, Arai H, Hosaka T, Takahashi A, Yoshimoto K. Nakaya Y
  • Journal Title: Biochim Biophys Acta 1791 Pages: 39-52
  • NAID: 120006631417
  • Peer Reviewed
• [Journal Article] Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas (2009)
  • Author(s): Qian ZR, Asa SL, Siomi H, Siomi MC, Yoshimato K, Yamada S, Wang EL, Rahman MM, Inoue H, Itakura M, Kudo E, Sano T
  • Journal Title: Mod Pathol 22 Pages: 431-441
  • Peer Reviewed
• [Journal Article] Expression of pl8(INK4C)is Down-regulated in Human Pituitary Adenomas (2009)
  • Author(s): Hossain MG, Iwata T, Mizusawa N, Qian ZR, Shima SW, Okutsu T, Yamada S, Sano T, Yoshimoto K
  • Journal Title: Endocr Pathol 20 Pages: 114-121
  • Peer Reviewed
• [Journal Article] Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas. (2009)
  • Author(s): Qian ZR, et al.
  • Journal Title: Mod Pathol 22 Pages: 431-441
  • Peer Reviewed
• [Journal Article] Identification of cis-acting promoter sequences required for expression of the glycerol-3-phosphate acyltransferase 1 gene in mice. (2009)
  • Author(s): Yoshida M, et al.
  • Journal Title: Biochim Biophys Acta 1791 Pages: 39-52
  • Peer Reviewed
• [Journal Article] The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas (2008)
  • Author(s): Leoatiou CA, Gueorguiev M, van der Spuy J, Quinton R, Lolli F, Hassan S, Chahal HS, Igreja SC, Jordan S, Rowe J, Stolbrink M, Christian HC, Wray J, Bishop-Bailey D, Berney DM, Wass JA, Popovic V, Ribeiro-Oliveira A Jr, Gadelha MR, Monson JP, Akker SA, Davis JR, Clayton RN, Yoshimoto K, Iwata T, Matsuno A, Eguchi K, Musat M, Flanagan D, Peters G, Bolger GB, Chapple JP, Frohman LA, Grossman AB, Korbonits M
  • Journal Title: J Clin Endocrinol Metab 93 Pages: 2390-2401
  • Peer Reviewed
• [Journal Article] Role of cyclin-dependent kinase inhibitors in pituitary tumorigenesis : an update (2008)
  • Author(s): Md. Golam Hossain, Takeo Iwata, Noriko Mizusuwa, Shozo Yamada, Qian Zhi Rong, Toshiaki Sano, Katsuhiko Yoshimato(Yoshida M, Harada N, Yamamoto H, Taketani Y)
  • Journal Title: Shikoku Acta Medica 64 Pages: 226-231
  • NAID: 120006324296
  • Peer Reviewed
• [Journal Article] 家族性副甲状腺機亢進症として診断された家系におけるHRPT2遺伝子の解析 (2008)
  • Author(s): 水澤典子
  • Journal Title: 四国歯学会雑誌 20 Pages: 229-234
• [Journal Article] アディポサイトカインと生活習慣病 (2008)
  • Author(s): 吉本勝彦、岩田武男、水澤典子
  • Journal Title: 四国歯学会雑誌 20 Pages: 261-263
  • NAID: 120005821557
• [Journal Article] The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. (2008)
  • Author(s): Leontiou CA, et al.
  • Journal Title: J Clin Endocrinol Metab 93 Pages: 2390-2401
  • Peer Reviewed
• [Journal Article] The Role of the AIP Gene in Familial and Sporadic Pituitary Adenomas. (2008)
  • Author(s): Leontiou GA, et. al.
  • Journal Title: J CIin Endocrinol Metab [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] A case of hyperparathyroidism-jaw tumour syndrome found in the treatment of an ossifying fibroma in the marlllary bone (2007)
  • Author(s): Yamashita Y, Akiyama T, Mizusarva N, Yoshimato K. Goto M
  • Journal Title: Int J Oral Maxillofac Surg 36 Pages: 365-369
  • Peer Reviewed
• [Journal Article] The aryl hydrocarbon receptor-interacting protein gene is rarely mutated in sporadic GH-secreting adenomas (2007)
  • Author(s): Iwata T, Yamada S, Mizusawa N, Golam HM, Sano T, Yashimoto K
  • Journal Title: Clin Endocrinol(Oxf) 66 Pages: 499-542
  • NAID: 120005708873
  • Peer Reviewed
• [Journal Article] A Growth Hormone Receptor Mutation Impairs Growth Hormone Autofeedback Signaling in Pituitary Tumors (2007)
  • Author(s): Sylvia L Asa, Rebecca DiGiovanni, Jing Jiang, Megan L Ward, Kimberly Loesch, Shaza Yamada, Yoshiaki Sano, Katsuhiko Yashimoto, Stuart J. Frank, Schereen Ezzat
  • Journal Title: Cancer Res 67 Pages: 7505-7511
  • Peer Reviewed
• [Journal Article] Parafibromin tumor supressor enhances cell growth in the cells expressing SV40 large T antigen (2007)
  • Author(s): Iwata T, Mizusawa N, Taketani Y, Itakura M, Yoshimoto K
  • Journal Title: Oncogene 26 Pages: 6176-6183
  • Peer Reviewed
• [Journal Article] Tumor-specific down-regulation and methylation of the CDH13(H-cadherin) and CDH1(E-cadherin)genescorrelate with aggressivess of human pituitary adenomas (2007)
  • Author(s): Zhi Rong Qian, Yoshiaki Sana, Katsuhiko Yoshimoto, Sylvia L Asa, Shozo Yamada, Noriko Mizusawa, Eiji Kudo
  • Journal Title: Mod Pathol 20 Pages: 1269-1277
  • Peer Reviewed
• [Journal Article] 癌抑制因子パラフィプロミンはSV401arge T抗原存在下では細胞増殖促進に働くホルモンと臨床2008冬季増刊号「内分泌病理学最近の進歩2007」 (2007)
  • Author(s): 岩田武男、水澤典子、Hossain Md. Golam、吉本勝彦
  • Journal Title: 医学の世界社 Pages: 147-155
• [Journal Article] Tumor-specific down-regulation and methylation of the CDH 13(H-cadherin)and CDH1(E-cadherin)genes correlate with aggressiveness of human pituitary adenomas (2007)
  • Author(s): Qian ZR, et. al.
  • Journal Title: Mod Pathol 20 Pages: 1269-1277
  • Peer Reviewed
• [Journal Article] A Growth Hormone Receptor Mutation Impairs Growth Hormone Autofeedback Signaling in Pituitary Tumors (2007)
  • Author(s): Asa SL, et. al.
  • Journal Title: Cancer Res 67 Pages: 7505-7511
  • Peer Reviewed
• [Journal Article] The aryl hydrocarbon receptor-interacting protein gene is rarely mutated in sporadic GH-secreting adenomas (2007)
  • Author(s): Iwata T, et. al.
  • Journal Title: Clin Endocrinol(Oxf) 66 Pages: 499-502
  • NAID: 120005708873
  • Peer Reviewed
• [Presentation] Compressive force-induced inhibition of adipocyte differentiation is mediated through down-regulatioin of PPARy2 (2008)
  • Author(s): Md. Golam Hossain, Takeo Iwata, Noriko Mizusawa, Katsuhiko Yoshimoto
  • Organizer: The International Symposium on"Oral Sciences to Improve The Quality of Life"
  • Place of Presentation: Tokushima, Japan
  • Year and Date: 2008-09-06
• [Presentation] Effect of Liver X Receptor(LXR)Agonist on GLP-1 Expression (2008)
  • Author(s): Wan Nazatul Shima, Noriko Mizusawa, Takeo Iwata, Katsuhiko Yoshimoto
  • Organizer: The International Symposium on"Oral Sciences to Improve The Quality of Life"
  • Place of Presentation: Tokushima, Japan
  • Year and Date: 2008-09-06
• [Presentation] Mutations, gene expression and CpG methylation status of cyclin-dependent kinase inhibitor P18INK4C in human pituitary adenomas. (2008)
  • Author(s): Hossain Md. Golam, et al.
  • Organizer: 第237回 徳島医学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2008-08-03
• [Presentation] YKL-40とMMP-1は脂肪組織のリモデリングに関与する (2008)
  • Author(s): 岩田武男=水澤典子, 板倉光夫, 吉本勝彦
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] isletasinの機能解析 (2008)
  • Author(s): 安永佳世, 水澤典子, 畠山節子, 査杢勝彦
  • Organizer: 第50回歯科基礎医学会学術大会・総会
  • Place of Presentation: 東京
• [Presentation] インクレチン発現におけるLXR合成アゴニストの影響 (2008)
  • Author(s): 小野信二, ワン・ナザトル・シマ, 水澤典子, 吉本勝彦
  • Organizer: 第50回歯科基礎医学会学術大会・総会
  • Place of Presentation: 東京
• [Presentation] LXRアゴニストによるインクレチン発現への影響 (2008)
  • Author(s): 水澤典子、岩田武男、吉田勝彦
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] 家族性副甲状腺機能亢進症家系および家族性下垂体腺腫家系におけるp27Kip1遺伝子解析 (2008)
  • Author(s): 吉田勝彦, Hossain Golam, 岩田武男, 水澤典子, 内野眞也, 鈴木やすよ, 水越常徳, 田原英樹, 櫻井晃洋, 紅粉睦男, 八代享, 鈴木眞一, 松野彰, 西岡宏, 田村哲郎
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] Mutational analysis and gene expression profile of CDKN2C/pl8INK4C in pituitary adenomas (2007)
  • Author(s): Hussain Md. Golam, Takao Iwata, Noriko Mizusawa Shozo Yamada, Qian Zhi Rong, Tashiaki Sano, Katsuhiko Yoshimoto
  • Organizer: The 2nd International Symposiunm on"The Fukure Direction of Oral Sciences in the 21st Ccntury"-Oral Sciences for Our Healthy Life-
  • Place of Presentation: Tokushima
  • Year and Date: 2007-12-08
• [Presentation] Reduced expression of the let-7 microRNAs in human pituitary adenomas in association with pituitary tumorlgenesis through regulating HMGA2 (2007)
  • Author(s): Qian Zhi Rong, Sano Toshiaki, Yamada Shozo, Yun Feng Yuan, Yoshimoto Katsuhiko, Kudo Eiji
  • Organizer: 第11回日本内分泌病理学会学術総会
  • Place of Presentation: 札幌
• [Presentation] The pi-class glutathione S-transferase(GSTP1)may be a novel tumor suppressor gene in pituitary turnorigenesis (2007)
  • Author(s): Yun Feng Yuan, Qian Zhi Rong, Sano Toshiaki, Yoshimoto Katsuhiko, Yamada Shozo, Kudo Eiji
  • Organizer: 第11回日本内分泌病理学会学術総会
  • Place of Presentation: 札幌
• [Presentation] マクロファージ培養上清が脂肪前駆細胞株SGBSのMMP発現に与える影響」 (2007)
  • Author(s): 岩田武男,水澤典子, 板倉光夫, 吉本勝彦
  • Organizer: 第28回日本肥満学会
  • Place of Presentation: 東京
• [Presentation] 「新規グリセロール-3-リン酸アシルトランスフェラーゼ(xGPAT1)の遺伝子クローニング」 (2007)
  • Author(s): 吉田将紀, 原田永勝, 原小百合, 伊雲潔, 吉本勝彦, 中屋豊
  • Organizer: 第28回日本肥満学会
  • Place of Presentation: 東京
• [Presentation] 「副甲状腺癌抑制因子パラフィプロミンはSV40 1arge T抗原存在下では細胞増殖促進に働く」 (2007)
  • Author(s): 岩田武男, 水澤典子, 竹谷豊, 板倉光夫, 吉本勝彦
  • Organizer: 第32回日本比較内分泌学会大会
  • Place of Presentation: 日光
• [Presentation] isletasin遺伝子の膵β細胞特異的発現と細胞内局在 (2007)
  • Author(s): 水澤典子, 畠山節子, 吉本勝彦
  • Organizer: 第49回歯科基礎医学会学術大会・総会
  • Place of Presentation: 札幌
• [Presentation] 家族性および孤発性GH産生腺腫におけるAIP遺伝子解析 (2007)
  • Author(s): 岩田武男, 山田正三, 水澤典子, ホサインゴラム、西岡宏, 松野彰、佐野壽昭, 吉本勝彦
  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Presentation] 膵β細胞に高発現するisletasin遺伝子の解析 (2007)
  • Author(s): 水澤典子、岩田武男、吉本勝彦
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台