2001 Fiscal Year Annual Research Report

ヒト消化器癌の発癌と進展におけるDNA修復酵素遺伝子の意義に関する研究

Research Project

Project/Area Number	12470263
Research Institution	Saga Medical School
Principal Investigator	宮崎耕治佐賀医科大学, 医学部, 教授 (30159173)
Co-Investigator(Kenkyū-buntansha)	北原賢二佐賀医科大学, 医学部, 助手 (30264162) 北島吉彦佐賀医科大学, 医学部, 助手 (30234256)
Keywords	胃癌 / 胆道癌 / 肝細胞癌 / MGMT / hMLH1 / GC-AT transiton / Hypermethylation / 予後予測
Research Abstract	胆嚢癌切除標本を用いてMGMTおよびミスマッチ修復酵素hMLH1の発現減弱を免疫組織学的に解析したところ、MGMT発現減弱(Mer-)かつhMLH1陰性の場合、最も予後不良となることを報告した。研究目的であるGC-AT transitionによるmutationを受ける癌悪性度に関わる遺伝子変異を検索した。胆嚢癌切除標本の癌部よりDNAを抽出した後、k-ras, b-カテニン遺伝子のmutation解析を行った。その結果、30例中、k-ras, b-カテニンのmutationが判明したものは、それぞれ3例、1例と予想外に低頻度であった。MutationのパターンはGC-AT transitionが4例中3例に認められたが、MGMTおよびhMLH1発現減弱には関連性を認めなかった。現在、他の候補遺伝子(P53,E-カドヘリン)に焦点を絞り、mutation解析を行っている。肝臓癌においては、切除標本中のMGMTの発現減弱がプロモーターのメチル化に起因していることを分子生物学的手法を用いて明らかにし、我々の推測と合致する結果を得た。現在、肝臓癌で高頻度で遺伝子変異が認められるb-カテニンをMer-の標的遺伝子と予測してmutation解析を進めている。また、胃癌において、MGMTおよびhMLH1, hMSH2の発現は癌の進行とともに減弱することを明らかにした。この結果より、癌進展に伴い、エピジェネテイツク制御機序が破綻していく可能性が推測された。以上、(1)MGMTかつhMLH1,hMSH2の発現減弱が胆嚢癌、肝臓癌、胃癌の予後不良因子となること、(2)肝臓癌において、MGMT発現減弱はプロモーターのメチル化に起因すること、(3)胆嚢癌においては、Mer-を契機にGC-AT変異がもたらされる標的遺伝子としては、k-ras, b-カテニン以外の他遺伝子の存在が考えられた。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] N.Kohya: "Deficient Expression of O_6,-Methylguanin-DNA Methyltransferase (MGMT) Combined with Mismatsh Repair Proteins hMLH1 and hMSH2 are Related to Poor Prognosis in Human Biliary Tract Carcinoma"Ann Surg Oncol. (in press).
[Publications] M.Tanaka: "Abnormal Expression of E-cadherin and β-catenin may be a Biomarker of Submucosal Invation and Lymph Node Metastasis : Impairment of Cell-Cell Adhesion Molecules Differs Between Two Histologic Typers of Early Gastric Cancer"Br J Surg. 89. 236-244 (2002)
[Publications] W.Jiao: "Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo"Br J Cancer. 86. 98-101 (2002)
[Publications] 宮崎耕治: "消化器癌におけるDNA修復機構とその破綻の関与"外科治療. 86・1. 108-109 (2002)
[Publications] S.Matsukura: "Deficient Expression of O_6-methylguanine-DNA methyltransferease correlates with prognostis in Hepatocellular, Gastric and Breast Cancers"Ann Surg Oncol. 8・10. 807-816 (2001)
[Publications] W.Jiao: "Exogenous Expression of E-cadherin in Gallbradder Carcinoma Cell Line G-415 Restores Its Cellular Polarity and Differentiation"Int J Oncol. 19. 1099-1107 (2001)
[Publications] S.Mukai: "The Role of E-cadheririn in the Differentiation of Gallbladder Cancer Cells"Cell Tissue Res. 306. 117-128 (2001)
[Publications] Y.Chen: "Critical role of typelV collagen in the growth of bile duct carcinoma. -In vivo and in vitro studies"Pthol Res Pract. 197. 585-596 (2001)
[Publications] Y.Sakamoto: "Combined Evaluation of NGF and p75NGFR expressions is a biomarker for predicting prognosis in human invasive ductal breast carcinoma"Oncol Rep. 8. 973-980 (2001)
[Publications] A.kuwahara: "Expression of melnoma Antigen-Encoding gene-1 Predicts lymph node Involvement in Early Gastric Carcinomas"Dig Dis Sci. 46. 262-267 (2001)
[Publications] Y.Sakamoto: "Expression of Trk tyrosin kinase receptor is a biologic marker for Proliferation and perineural invasion of human pancreatic ductal adenocarcinoma"Oncol Rep. 8. 477-484 (2001)
[Publications] T.Shimonishi: "Expression of endogenous galectin-1 and galectin-3 in intrahepatic Cholamgiocarcinoma"Hum Pathol. 32・3. 302-310 (2001)
[Publications] G.Edakuni: "Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in Cancer Front in breast carcinoma"Pathol Internat. 51. 172-178 (2001)

2001 Fiscal Year Annual Research Report

ヒト消化器癌の発癌と進展におけるDNA修復酵素遺伝子の意義に関する研究

Principal Investigator

宮崎 耕治 佐賀医科大学, 医学部, 教授 (30159173)

Research Products

[Publications] N.Kohya: "Deficient Expression of O_6,-Methylguanin-DNA Methyltransferase (MGMT) Combined with Mismatsh Repair Proteins hMLH1 and hMSH2 are Related to Poor Prognosis in Human Biliary Tract Carcinoma"Ann Surg Oncol. (in press).

[Publications] M.Tanaka: "Abnormal Expression of E-cadherin and β-catenin may be a Biomarker of Submucosal Invation and Lymph Node Metastasis : Impairment of Cell-Cell Adhesion Molecules Differs Between Two Histologic Typers of Early Gastric Cancer"Br J Surg. 89. 236-244 (2002)

[Publications] W.Jiao: "Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo"Br J Cancer. 86. 98-101 (2002)

[Publications] 宮崎耕治: "消化器癌におけるDNA修復機構とその破綻の関与"外科治療. 86・1. 108-109 (2002)

[Publications] S.Matsukura: "Deficient Expression of O_6-methylguanine-DNA methyltransferease correlates with prognostis in Hepatocellular, Gastric and Breast Cancers"Ann Surg Oncol. 8・10. 807-816 (2001)

[Publications] W.Jiao: "Exogenous Expression of E-cadherin in Gallbradder Carcinoma Cell Line G-415 Restores Its Cellular Polarity and Differentiation"Int J Oncol. 19. 1099-1107 (2001)

[Publications] S.Mukai: "The Role of E-cadheririn in the Differentiation of Gallbladder Cancer Cells"Cell Tissue Res. 306. 117-128 (2001)

[Publications] Y.Chen: "Critical role of typelV collagen in the growth of bile duct carcinoma. -In vivo and in vitro studies"Pthol Res Pract. 197. 585-596 (2001)

[Publications] Y.Sakamoto: "Combined Evaluation of NGF and p75NGFR expressions is a biomarker for predicting prognosis in human invasive ductal breast carcinoma"Oncol Rep. 8. 973-980 (2001)

[Publications] A.kuwahara: "Expression of melnoma Antigen-Encoding gene-1 Predicts lymph node Involvement in Early Gastric Carcinomas"Dig Dis Sci. 46. 262-267 (2001)

[Publications] Y.Sakamoto: "Expression of Trk tyrosin kinase receptor is a biologic marker for Proliferation and perineural invasion of human pancreatic ductal adenocarcinoma"Oncol Rep. 8. 477-484 (2001)

[Publications] T.Shimonishi: "Expression of endogenous galectin-1 and galectin-3 in intrahepatic Cholamgiocarcinoma"Hum Pathol. 32・3. 302-310 (2001)

[Publications] G.Edakuni: "Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in Cancer Front in breast carcinoma"Pathol Internat. 51. 172-178 (2001)

宮崎耕治佐賀医科大学, 医学部, 教授 (30159173)