Analysis of physiological function of vaults

• Project/Area Number: 19590314
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kagoshima University
• Principal Investigator: AKIYAMA Shinichi Kagoshima University, 大学院・医歯学総合研究科, 教授 (60117413)
• Co-Investigator(Kenkyū-buntansha): CHE Xiao-fang 鹿児島大学, 大学院・医歯学総合研究科, 助教 (10437973)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: MVP / Vault / LRP / osmotic stress / PI3K / Akt / 高浸透圧 / ARK / PTEN / アポトーシス / P38 / ストレス

Research Abstract

Vaultは、細胞内で一番大きなリボ核蛋白体であるが、その生理機能は現在まで不明である。今回の研究で、大腸癌細胞に高浸透圧ストレスを加えると、MVPの発現が亢進すること、MVPが発現した細胞は、高浸透圧に対して耐性になることを見出した。
MVP の発現は、腎臓や腸管などの恒常的に浸透圧変化の大きい組織において認められている。腎臓の腎髄質細胞は、高濃度のNaClにさらされ、500mM以上の塩濃度になることもある。高い塩濃度はアポトーシスを誘導するが、細胞はvaultの発現を亢進することにより、高浸透圧によって誘導されるアポトーシスを回避している可能性がある。

Research Products

• [Journal Article] Cepharanthine is a potent reversal agent for MRP7 (ABGG10)-mediated multidrug resistance. (2009)
  • Author(s): Ying Zhou
  • Journal Title: Biochem Pharmacol (in press)
  • Peer Reviewed
• [Journal Article] Sensitization of ABCB1 overexpressing cells to chemoterapeutic agents by FG020326 via binding to ABCBl and inhibiting its function. (2009)
  • Author(s): Chun-ling Dai
  • Journal Title: Biochem Pharmacol (in press)
  • Peer Reviewed
• [Journal Article] Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU (2008)
  • Author(s): Zhao H-Y, Che X-F, Akiyama S(他12名)
  • Journal Title: Cancer Res 68 Pages: 7035-7041
  • Peer Reviewed
• [Journal Article] Hyperosmotic Stress Up-regulates the Expression of Major Vault Protein in SW620 Human Colon Cancer Cells. Exp (2008)
  • Author(s): Ikeda R, Che X-F, Akiyama S(他16名)
  • Journal Title: Cell Res 314 Pages: 3017-3026
  • Peer Reviewed
• [Journal Article] Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in KM12C cells (2008)
  • Author(s): Zhao H-Y, Che X-F, Akiyama S(他12名)
  • Journal Title: Cancer Lett. 270 Pages: 156-163
  • Peer Reviewed
• [Journal Article] Copper Transport Systems are Involved in Multidrug Resistance and Drug Transport (2008)
  • Author(s): Furukawa T, Akiyama S(他3名)
  • Journal Title: Curr Med Chem 15 Pages: 3268-3278
  • Peer Reviewed
• [Journal Article] Suppression of the proliferation of cancer cell lines, KB-3-1 and K562 cells preceded by a decrease in intracellular pH caused by phenoxazine derivatives (2008)
  • Author(s): Che X-F, Akiyama S, Tomoda A
  • Journal Title: Oncol Rep 19 Pages: 1253-1258
  • Peer Reviewed
• [Journal Article] Thymidine phosphorylase inhibits the expression of proapoptic protein BNIP3 (2008)
  • Author(s): Ikeda R, Che X-F, Akiyama S(他13名)
  • Journal Title: Biochem Biophys Res Commun 370 Pages: 220-224
  • Peer Reviewed
• [Journal Article] Anti-angiogenic effect of 5-Fluorouracil-based drugs against human colon cancer xenografts (2008)
  • Author(s): Ooyama A, Akiyama S(他4人)
  • Journal Title: Cancer Lett 267 Pages: 26-36
  • Peer Reviewed
• [Journal Article] Apoptosis induction preceded by mitochondrial depolarization in multiple myeloma cell line U266 by 2-aminophenoxazine-3-one (2008)
  • Author(s): Shirato K, Che X-F, Akiyama S(他5人)
  • Journal Title: Biol Pharm Bull 31 Pages: 62-67
  • NAID: 110006569975
  • Peer Reviewed
• [Journal Article] Alterations in the glycoform of cisplatin-resistant human carcinoma cells are caused by defects in the endoplasmic reticulum-associated degradation system (2008)
  • Author(s): Nakagawa H, Akiyama S(他11人)
  • Journal Title: Cancer lett 270(2) Pages: 295-301
  • Peer Reviewed
• [Journal Article] Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU (2008)
  • Author(s): Hong-Ye Zhao
  • Journal Title: Cancer Res. 68 Pages: 7035-7041
  • Peer Reviewed
• [Journal Article] Hyperosmotic stress Up-regulates the Expression of Major Vault Protein in SW620 Human Colon Cancer Cells. (2008)
  • Author(s): Ryuji Ikeda
  • Journal Title: Exp. Cell Res. 314 Pages: 3017-3026
  • Peer Reviewed
• [Journal Article] Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in KM12C cells. (2008)
  • Author(s): Hona-Ye Zhao
  • Journal Title: Cancer Lett. 270 Pages: 156-163
  • Peer Reviewed
• [Journal Article] Copper transport systems are involved in multidrug resistance and drug transport. (2008)
  • Author(s): Furukawa T
  • Journal Title: Curr Med Chem. 15 Pages: 3268-3278
  • Peer Reviewed
• [Journal Article] Suppression of the proliferation of cancer cell lines, KB-3-1 and K562 cells preceded by a decrease in intracellular pH caused by phenoxazine derivatives. (2008)
  • Author(s): Xiao-Fang Che
  • Journal Title: Oncol Rep. 19 Pages: 1253-1258
  • Peer Reviewed
• [Journal Article] Thymidine phosphorylase inhibits the expression of proapoptic protein BNIP3. (2008)
  • Author(s): Ryuji Ikeda
  • Journal Title: Biochem Biophys Res Commun. 370 Pages: 220-224
  • Peer Reviewed
• [Journal Article] Anti-angiogenic effect of 5-Fluorouracil-based drugs against human colon cancer xenografts (2008)
  • Author(s): Akio Ooyama
  • Journal Title: Cancer Lett. 267 Pages: 26-36
  • Peer Reviewed
• [Journal Article] Apoptosis induction preceded by mitochondrial depolarization in multiple myeloma cell line U266 by 2-aminophenoxazine-3-one. (2008)
  • Author(s): Ken Shirato
  • Journal Title: Biol Pharm Bull. 31 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Alterations in the glycoform of cisplatin-resistant human careinoma cells are caused by defects in the endoplasmic reticulu m-associated degradation system. (2008)
  • Author(s): Hiroaki Nakagawa
  • Journal Title: Cancer lett 270 Pages: 295-301
  • Peer Reviewed
• [Journal Article] Apoptosis induction preceded by mitochondrial depolarization in multiple myeloma cell line U266 by 2-aminophenoxazine-3-one. (2008)
  • Author(s): Shirato K
  • Journal Title: Biol Pharm Bull. 31 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Copper-Transporting P-Type ATPase, ATP7A, Confers Multidrug Resistance and Its Expression Is Related to Resistance to SN-38 in Clinical Colon Cancer (2007)
  • Author(s): Owatari S, Che X-F, Akiyama S(他12人中)
  • Journal Title: Cancer Res 67 Pages: 4860-4868
  • Peer Reviewed
• [Journal Article] Reversal of P-Glycoprotein-Mediated Multidrug Resistance by Sipholane Triterpenoids (2007)
  • Author(s): Jain S, Akiyama S(他6人)
  • Journal Title: J. Nat. Prod 70 Pages: 928-931
  • Peer Reviewed
• [Journal Article] Involvement of Mitogen-activated protein kinase signaling pathways in microcystin-LR-induced apoptosis after its selective uptake mediated by OATP1B1 and OATP1B3 : microcystin-lr induces the apoptosis via mapk (2007)
  • Author(s): Komatsu M, Akiyama S(他6人)
  • Journal Title: Toxicol. Sci 97 Pages: 407-416
  • Peer Reviewed
• [Journal Article] ABCB6 Localizes toboth the outer mutocondrial membrane and the plasma membrane (2007)
  • Author(s): Jill K. Paterson, Akiyama S(他11人)
  • Journal Title: Biochemistry 33 Pages: 9443-9452
  • Peer Reviewed
• [Journal Article] Reversal effect of BM-cyclin 1 on multidrug resistance in C-A120 cells (2007)
  • Author(s): Wang L, Akiyama S(他4人)
  • Journal Title: Anti-cancer Drug 18 Pages: 1015-1021
  • Peer Reviewed
• [Journal Article] Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells (2007)
  • Author(s): Tachiwada T, Che X-F, Akiyama S(他10人)
  • Journal Title: Oncol Rep 18 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer. (2007)
  • Author(s): Owarari S
  • Journal Title: Cancer Res. 67 Pages: 4860-4868
  • Peer Reviewed
• [Journal Article] Involvement of mitogen-activated protein kinase signaling pathways in microcystin-LR-induced apoptosis after its selective uptake mediated by OATP1B1 and OATP1B3. (2007)
  • Author(s): Komatsu M
  • Journal Title: Toxicol Sci. 97 Pages: 407-416
  • Peer Reviewed
• [Journal Article] Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells. (2007)
  • Author(s): Tachiwada T
  • Journal Title: Oncol Rep. 18 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Cepharanthine is a potent reversal agent for MRP7 (ABGG10)-mediated multidrug resistance
  • Author(s): Ying Zhou, Shin-ichi Akiyama(他11人)
  • Journal Title: Biochem Pharmacol (in press)
  • Peer Reviewed
• [Journal Article] Anti-angiogeneic effect of 5-fluorouracil-based drugs against human colon cancer xenografts
  • Author(s): Ooyama A
  • Journal Title: Cancer Letters (In press)
  • Peer Reviewed
• [Journal Article] Suppression of the proliferation of cancer cell lines, KB-3-1 and K562 cells preceded by a decrease in intracellular pH caused by phenoxazine derivatives
  • Author(s): Che X-F
  • Journal Title: Oncol Rep (In press)
  • Peer Reviewed
• [Journal Article] Thymidine Phosphorylase inhibits the expression of proapoptotic protein BNIP3
  • Author(s): Ikeda R
  • Journal Title: Biochem Biophys Res Commun. (In press)
  • Peer Reviewed
• [Presentation] Gemcitabinenの耐性と核酸輸送蛋白質 (2008)
  • Author(s): 古川龍彦
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学大会合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2008-12-09
• [Presentation] チミジンホスホリラーゼ発現腫瘍細胞におけるNF-κBを介したIL-8の発現亢進機講 (2008)
  • Author(s): 田畑祥
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議
  • Year and Date: 2008-10-29
• [Presentation] ヒト大腸癌における5-FUによる血管新生阻害因子TSP-1の誘導 (2008)
  • Author(s): 趙紅業
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] 膵癌細胞株MIAPaCa-2由来Gemcitabine耐性細胞の耐性機構の解析 (2008)
  • Author(s): 古川龍彦
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] survivinペプチド(89-104アミノ酸)によるATL細胞のアポトーシス誘導 (2008)
  • Author(s): 車暁芳
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] 低酸素によるヒト線維芽細胞でのPGISの高発現 (2008)
  • Author(s): 王嘉
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] チミジンホスホリラーゼ発現腫瘍細胞におけるNF-κBを介したIL-8の発現完進機講 (2008)
  • Author(s): 田畑 祥
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] ヒト大腸癌における5-FUによる血管新生阻害因子TSP-1の誘導 (2008)
  • Author(s): 趙 紅業
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] 膵癌細胞株MIAPaCa-2由来Gemcitabine耐性細胞の耐性機構の解析 (2008)
  • Author(s): 古川龍彦
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] survivinペプチド(89-104アミノ酸)によるATL細胞のアポトーシス誘導 (2008)
  • Author(s): 車 暁芳
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] 低酸素によるヒト線維芽細胞でのPGISの高発現 (2008)
  • Author(s): 王 嘉
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] 腫瘍微小血管に対する5-FUとその活性化酵素の作用 (2008)
  • Author(s): 秋山伸一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] p53R2標的siRNAは悪性黒色の腫瘍増殖を抑制して抗癌剤感受性を高める (2008)
  • Author(s): 松下茂人
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] 腫瘍微小血管に対する5-FUとその活性化酵素の作用 (2008)
  • Author(s): 秋山伸一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-28
• [Presentation] p53R2標的siRNAは悪性黒色の腫瘍増殖を抑制して抗癌剤感受性を高める (2008)
  • Author(s): 松下茂人
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-28
• [Presentation] 膵癌細胞株MIAPaCa-2由来Gemcitabine耐性細胞の耐性機構の解析 (2008)
  • Author(s): 古川龍彦
  • Organizer: 第12回がん分子標的治療研究会総会
  • Place of Presentation: 学術総合センター(東京)
  • Year and Date: 2008-06-27
• [Presentation] 弾癌細胞株MIAPaCa-2由来Gemcitabine耐性細胞の耐性機構の解析 (2008)
  • Author(s): 古川龍彦
  • Organizer: 第12回がん分子標的治療研究会総会
  • Place of Presentation: 学術総合センター(東京都)
  • Year and Date: 2008-06-27
• [Presentation] がん微小環境と抗がん剤 (2008)
  • Author(s): 秋山伸一
  • Organizer: 第29回癌免疫外科研究会
  • Place of Presentation: ホテル日航東京(東京都)
  • Year and Date: 2008-06-20
• [Presentation] 第29回癌免疫外科研究会 (2008)
  • Author(s): 秋山伸一
  • Place of Presentation: ホテル日航東京
  • Year and Date: 2008-06-19
• [Presentation] Gemcitabinenの耐性と核酸輸送蛋白質第31回日本分子生物学会年会 (2008)
  • Author(s): 古川龍彦
  • Organizer: 第81回日本生化学大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 籃藻毒マイクロシスチンLRの肝臓特異的毒性の発現機構第30回日本分子生物学学会年会・第80回日本生化学大会 (2007)
  • Author(s): 小松正治
  • Organizer: 合同大会
  • Place of Presentation: パシフィコ横浜ヨコハマグランドインンターコンチネンタルホテル
  • Year and Date: 2007-12-14
• [Presentation] 籃藻毒マイクロシスチンLRの肝臓特異的毒性の発現機構 (2007)
  • Author(s): 小松正治
  • Organizer: 第30回日本分子生物学学会年会・第80回日本生化学大会 合同大会
  • Place of Presentation: パシフィコ横浜ヨコハマグランドインンターコンチネンタルホテル
  • Year and Date: 2007-12-14
• [Presentation] 銅輸送体ATP7A発現による抗癌剤耐性の機構第30回日本分子生物学学会年会・第80回日本生化学大会 (2007)
  • Author(s): 古川龍彦
  • Organizer: 合同大会
  • Place of Presentation: パシフィコ横浜ヨコハマグランドインンターコンチネンタルホテル
  • Year and Date: 2007-12-11
• [Presentation] 銅輸送体ATP7A発現による抗癌剤耐性の機構 (2007)
  • Author(s): 古川龍彦
  • Organizer: 第30回日本分子生物学学会年会・第80回日本生化学大会 合同大会
  • Place of Presentation: パシフィコ横浜ヨコハマグランドインンターコンチネンタルホテル
  • Year and Date: 2007-12-11
• [Presentation] Anti-angiogenic effect of 5-fluorouacil based drug against human colon cancer xenograft (2007)
  • Author(s): Akio Ooyama
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-05
• [Presentation] Thymidine phosphorylase suppresses the expression of proapoptic protein BNIP3 (2007)
  • Author(s): Ryuji Ikeda
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-05
• [Presentation] Thymidine phosphorylase suppresses the expression of proapoptic protein BNIP3. (2007)
  • Author(s): Ryuji Ikeda
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-05
• [Presentation] Anti-angiogenic effect of 5-fluorouacil based drug against human colon cancer xenograft. (2007)
  • Author(s): Akio Ooyama
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-05
• [Presentation] The effect of thymidine phosphorylase, 5-FU and hypoxia on tumor microenvironments.(シンポジウム) (2007)
  • Author(s): Shin-chi Akiyama
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] A copper transporter ATP7A mediate multidrug resistance and the vesicle transport system (2007)
  • Author(s): Tatsuhiko Furukawa
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] The effect of thymidine phosphorylase, 5-FU and hypoxia on tumor microenvironments.(シンポジウム) (2007)
  • Author(s): Shin-chi Akiyama
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] A copper transporter ATP7A mediate multidrug resistance and the vesicle transport system. (2007)
  • Author(s): Tatsuhiko Furukawa
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] Induction of angiogenesis inhibitor thrombospondin-1 by 5-FU in human colon cancer cells (2007)
  • Author(s): Hong-Ye Zhao
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Increased expression of PGIS in two human fibroblast cell lines under hypoxic condition (2007)
  • Author(s): Jia Wang
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Molecular basis for the induction of interleukin-8 by thmidine phosphorylase (2007)
  • Author(s): Sho Tabata
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] The effect of hypoxia on gene expression in human fibroblast WI-38 cells (2007)
  • Author(s): Xiao-Fang Che
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Induction of angiogenesis inhibitor thrombospondin-1 by 5-FUin human colon cancer cells. (2007)
  • Author(s): Hong-Ye Zhao
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Increased expression of PGIS in two human fibroblast cell lines under hypoxic condition. (2007)
  • Author(s): Jia Wang
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Molecular basis for the induction of interleukin-8 by thmidine phosphorylase. (2007)
  • Author(s): Sho Tabata
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] The effect of hypoxia on gene expression in human fibroblast WI-38 cells. (2007)
  • Author(s): Xiao-Fang Che
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Book] 日本臨床がん薬物療法学(増刊号) (2009)
  • Author(s): 秋山伸一
• [Book] がん薬物療法学 増刊号 (2009)
  • Author(s): 秋山伸一
  • Total Pages: 5
  • Publisher: 日本臨床
• [Book] 消化器がん化学療法 (2008)
  • Author(s): 秋山伸一
  • Publisher: 日本メディカルセンター
• [Book] 消化器がん化学療法2008 (2008)
  • Author(s): 秋山伸一
  • Total Pages: 7
  • Publisher: 日本メディカルセンター
• [Book] 消化器がん化学療法2008(共著) (2008)
  • Author(s): 秋山伸一
  • Total Pages: 7
  • Publisher: 株式会社 日本メディカルセンター