2000 Fiscal Year Annual Research Report

転写因子ets-1を介した糖転移酵素GnT-Vの癌転移、浸潤メカニズムの解明

Research Project

Project/Area Number	12215097
Research Institution	Osaka University
Principal Investigator	三善英知大阪大学, 医学系研究科, 助手 (20322183)
Keywords	Ets-1 / GnT-V / 癌転移 / 浸潤 / 大腸癌 / 膵臟癌 / プロテアーゼ
Research Abstract	研究計画に従い、転写因子ets-1を介した糖転移酵素GnT-Vの癌転移、浸潤メカニズムの解明の研究をin vitro,in vivoで行った。1999年にJBC274(22941-22948)に発表したデータをもとに膵癌を選択し、Ets-1,Ets-2,GnT-III,GnT-Vを恒久的に高発現する膵臓癌細胞(MIA-Pacall)を樹立した。これらの細胞の形態学的な変化は見られたが、in vitroでの細胞増殖速度は同じであった。これらをヌードマウスに移植して腫瘍の進展を検討したところ、Ets-2の過剰発現株は他の群に比べて有意に造腫瘍性が高かった。実際のヒト癌組織でEts-1,Ets-2,GnT-Vの発現を免疫組織化学法で検討したところ、大腸癌、膵臓癌ではこれらの発現は悪性度に相関して上昇したが、肝臓癌では未分化肝癌で発現が低下するため予後とは逆相関した(Clin Cancer Res 61772-1777,Am J Clin Pathol 114,719-25,Int.J.Cancer 77,in press)。この結果は各腫瘍によってGnT-Vのターゲットとなる糖タンパク質の基質分子が異なるためと考えられ、今後それらの同定と、基質分子における糖鎖の役割を明らかにしてゆく予定である。またets-1がプロテアーゼを活性化させ癌の浸潤に関与するという報告が以前よりあったが、GnT-Vを過剰発現した癌では、ある種のセリンプロテアーゼを活性化させることを見い出した(preparation for submission)。今後、この活性化が癌の転移に関与する機構を解明したい。

Research Products

(9 results)

All Other

All Publications (9 results)

[Publications] Ito Y et al.: "Ets-1 Expression in Extrahepatic Bile Duct Carcinoma and Cholangiocellular Carcinoma."Oncology . 58. 248-252 (2000)
[Publications] Murata K et al.: "Expression of N-acetylglucosaminyltransferase Vin colorectal cancer correlates with metastasis and poor prognosis."Clin Cancer Res. 6. 1772-1777 (2000)
[Publications] Gao C.X. et al.: "Purification and characterization of a lectin recognizing bisecting β-D-mannoside β1,4-N-acetylglucosamine structure : identified as a member of annexin family."Glycobiology. 10. 1209-1216 (2000)
[Publications] Takahashi,T. et al.: "Alpha1,6 fucosyltransferase is highly and specifically expressed in human ovarian serous adenocarcinomas."Int J Cancer. 88. 914-919 (2000)
[Publications] Ito Y et al.: "Expression and possible role of ets-1 in hepatocellular carcinoma."Am J Clin Pathol. 114. 719-725 (2000)
[Publications] Kitada,T et al.: "Addition of bisecting N-acetylglucosamine residues to E-cadherin downregulates the tyrosine phosphorylation of β-catenin."J.Biol.Chem.. 276. 475-480 (2001)
[Publications] Ito,Y et al.: "The elevated expression of UDP-N-acetylglucosamine : α mannoside β 1, 6 N-acetylglucosaminyltransferase (GnT-V) is an early event in hepatocar cinogenesis."Int.J.Cancer.. 77(in press). (2001)
[Publications] Hisamoto,K et al.: "Estrogen induces the Akt-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells."J.Biol.Chem.. 276(in press). (2001)
[Publications] Taniguchi,N et al.: "A glycomic approach to the identification and characterization of glycoprotein function cells transfected with glycolsyltransferase genes."Proteomics. 1(in press). (2001)

2000 Fiscal Year Annual Research Report

転写因子ets-1を介した糖転移酵素GnT-Vの癌転移、浸潤メカニズムの解明

Principal Investigator

三善 英知 大阪大学, 医学系研究科, 助手 (20322183)

Research Products

[Publications] Ito Y et al.: "Ets-1 Expression in Extrahepatic Bile Duct Carcinoma and Cholangiocellular Carcinoma."Oncology . 58. 248-252 (2000)

[Publications] Murata K et al.: "Expression of N-acetylglucosaminyltransferase Vin colorectal cancer correlates with metastasis and poor prognosis."Clin Cancer Res. 6. 1772-1777 (2000)

[Publications] Gao C.X. et al.: "Purification and characterization of a lectin recognizing bisecting β-D-mannoside β1,4-N-acetylglucosamine structure : identified as a member of annexin family."Glycobiology. 10. 1209-1216 (2000)

[Publications] Takahashi,T. et al.: "Alpha1,6 fucosyltransferase is highly and specifically expressed in human ovarian serous adenocarcinomas."Int J Cancer. 88. 914-919 (2000)

[Publications] Ito Y et al.: "Expression and possible role of ets-1 in hepatocellular carcinoma."Am J Clin Pathol. 114. 719-725 (2000)

[Publications] Kitada,T et al.: "Addition of bisecting N-acetylglucosamine residues to E-cadherin downregulates the tyrosine phosphorylation of β-catenin."J.Biol.Chem.. 276. 475-480 (2001)

[Publications] Ito,Y et al.: "The elevated expression of UDP-N-acetylglucosamine : α mannoside β 1, 6 N-acetylglucosaminyltransferase (GnT-V) is an early event in hepatocar cinogenesis."Int.J.Cancer.. 77(in press). (2001)

[Publications] Hisamoto,K et al.: "Estrogen induces the Akt-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells."J.Biol.Chem.. 276(in press). (2001)

[Publications] Taniguchi,N et al.: "A glycomic approach to the identification and characterization of glycoprotein function cells transfected with glycolsyltransferase genes."Proteomics. 1(in press). (2001)

三善英知大阪大学, 医学系研究科, 助手 (20322183)