2000 Fiscal Year Annual Research Report

膵癌の発生・進展に関与する遺伝子異常の解析

Research Project

Project/Area Number	12470043
Research Institution	Tohoku University
Principal Investigator	堀井明東北大学, 大学院・医学系研究科, 教授 (40249983)
Co-Investigator(Kenkyū-buntansha)	星雅人東北大学, 大学院・医学系研究科, 助手 (20323008) 福重真一東北大学, 大学院・医学系研究科, 講師 (90192723)
Keywords	膵がん / 遺伝子変異 / 12q / 17p / 18q / 1p / RIZ / MSI
Research Abstract	膵癌において高頻度に欠失の見られる領域のうち3か所(12q、17p、18q)の染色体欠失が予後不良と相関することを明らかにし、これらのうち膵の発癌過程で初期変化と考えられる18qにおける標的遺伝子と考えられるSMAD4遺伝子がホモに欠失している膵癌株に正常SMAD4遺伝子を導入しても増殖能は抑制されなかったことをふまえ、膵の前がん病変と位置づけられる粘液産成膵腫瘍(intraductal papillary-mucinous tumor、IPMT)を解析した。その結果、全くSMAD4の異常は見られず、18qにはSMAD4以外にもがん抑制遺伝子が局在する可能性が考えられた。膵癌はじめ、多くの腫瘍において異常が報告されている1p36-p35領域においてBACによるcontigを作成し、同領域の解析を進めた。同領域に局在するRIZ遺伝子を解析し、胃癌、大腸癌、子宮内膜癌などのMSI陽性の癌で高頻度に異常が見られるのみならず、これまでMSI陽性であって標的遺伝子の不明であった膵癌においても異常を同定し、これらの腫瘍における発がんの標的遺伝子である可能性が示唆された。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Saito,A. et al.: "p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1."J.Hum.Genet.. 45. 177-181 (2000)
[Publications] Yatsuoka,T. et al.: "Association of poor prognosis with loss of 12q, l7p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma."Am.J.Gastroent.. 95. 2080-2085 (2000)
[Publications] Ohira,M. et al.: "Identification and characterization of a 500-kb homozygously de1eted region at 1p36.2-p36.3 in a neuroblastoma cell line."Oncogene,. 19. 4302-4307 (2000)
[Publications] Nakagawara,A. et al.: "Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma."Med.Pediatr.Oncol.. 35. 516-521 (2000)
[Publications] Piao.Z. et al.: "Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability."Cancer Res.. 60. 4701-4704 (2000)
[Publications] Sakamoto,Y. et al.: "Molecular cloning and expression of cDNA encoding chicken UDP-GlcNAc : GlcNAcβ1-6 (GlcNAcβ1-2) Manα1-R [G1cNAc to Man] βl, 4N-acetylglucosaminyItransferase VI."J.Biol.Chem.. 275. 36029-36034 (2000)
[Publications] Shinoura,N. et al.: "Degree of apoptosis induced by adenovirus-mediated transduction of p53 or p73alpha depends on the p53 status of glioma cells."Cancer Lett.,. 160. 67-73 (2000)
[Publications] Sun,C.. et al.: "Characterization of the mutations of the K-ras, p53, p16, and SMAD4 genes in 15 human pancreatic cancer cell lines."Oncol.Rep.. 8. 89-92 (2001)
[Publications] Sakurada,K. et al.: "RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum."Genes Chromosomes Cancer. 30. 207-211 (2001)
[Publications] Schutte,B.C. et al.: "Report of the sixth international workshop on human chromosome 1 mapping 2000."Cytogenet.Cell Genet.. (in press).
[Publications] Youssef,E.M. et al.: "Human BAC contig covering the deleted region in pancreatic cancer at 12q21."DNA Seq.. (in press).
[Publications] Makino,N.et al.: "Isolation and characterization of the human gene homologous to the Drosophila Headcase (hdc) gene in chromosome bands 6q23-q24, a region of common deletion in human pancreatic cancer."DNA Seq.. (in press).
[Publications] Inoue,H. et al.: "Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis."Genes Chromosomes Cancer. (in press).
[Publications] Chen,Y.Z. et al.: "A BAC-based STS-content map spanning a 35-megabase region of human chromosome 1p35-36."Genomics. (in press).
[Publications] Kaneko,K. et al.: "Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis."J.Hum Genet.. (in press).
[Publications] Kondo,E. et al.: "The interacting domains of three MutL heterodimers in man : hMLH1 interacts with 36 homologous amino-acid residues within hMLH3, hPMS1, and hPMS2."Nucl.Acids Res.. (in press).

2000 Fiscal Year Annual Research Report

膵癌の発生・進展に関与する遺伝子異常の解析

Principal Investigator

堀井 明 東北大学, 大学院・医学系研究科, 教授 (40249983)

Research Products

[Publications] Saito,A. et al.: "p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1."J.Hum.Genet.. 45. 177-181 (2000)

[Publications] Yatsuoka,T. et al.: "Association of poor prognosis with loss of 12q, l7p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma."Am.J.Gastroent.. 95. 2080-2085 (2000)

[Publications] Ohira,M. et al.: "Identification and characterization of a 500-kb homozygously de1eted region at 1p36.2-p36.3 in a neuroblastoma cell line."Oncogene,. 19. 4302-4307 (2000)

[Publications] Nakagawara,A. et al.: "Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma."Med.Pediatr.Oncol.. 35. 516-521 (2000)

[Publications] Piao.Z. et al.: "Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability."Cancer Res.. 60. 4701-4704 (2000)

[Publications] Sakamoto,Y. et al.: "Molecular cloning and expression of cDNA encoding chicken UDP-GlcNAc : GlcNAcβ1-6 (GlcNAcβ1-2) Manα1-R [G1cNAc to Man] βl, 4N-acetylglucosaminyItransferase VI."J.Biol.Chem.. 275. 36029-36034 (2000)

[Publications] Shinoura,N. et al.: "Degree of apoptosis induced by adenovirus-mediated transduction of p53 or p73alpha depends on the p53 status of glioma cells."Cancer Lett.,. 160. 67-73 (2000)

[Publications] Sun,C.. et al.: "Characterization of the mutations of the K-ras, p53, p16, and SMAD4 genes in 15 human pancreatic cancer cell lines."Oncol.Rep.. 8. 89-92 (2001)

[Publications] Sakurada,K. et al.: "RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum."Genes Chromosomes Cancer. 30. 207-211 (2001)

[Publications] Schutte,B.C. et al.: "Report of the sixth international workshop on human chromosome 1 mapping 2000."Cytogenet.Cell Genet.. (in press).

[Publications] Youssef,E.M. et al.: "Human BAC contig covering the deleted region in pancreatic cancer at 12q21."DNA Seq.. (in press).

[Publications] Makino,N.et al.: "Isolation and characterization of the human gene homologous to the Drosophila Headcase (hdc) gene in chromosome bands 6q23-q24, a region of common deletion in human pancreatic cancer."DNA Seq.. (in press).

[Publications] Inoue,H. et al.: "Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis."Genes Chromosomes Cancer. (in press).

[Publications] Chen,Y.Z. et al.: "A BAC-based STS-content map spanning a 35-megabase region of human chromosome 1p35-36."Genomics. (in press).

[Publications] Kaneko,K. et al.: "Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis."J.Hum Genet.. (in press).

[Publications] Kondo,E. et al.: "The interacting domains of three MutL heterodimers in man : hMLH1 interacts with 36 homologous amino-acid residues within hMLH3, hPMS1, and hPMS2."Nucl.Acids Res.. (in press).

堀井明東北大学, 大学院・医学系研究科, 教授 (40249983)