2002 Fiscal Year Annual Research Report

p53とその標的遺伝子群の機能解析

Research Project

Project/Area Number	12213115
Research Institution	Sapporo Medical University
Principal Investigator	時野隆至札幌医科大学, 医学部, 教授 (40202197)
Keywords	p53 / p63 / p73 / 癌抑制遺伝子 / 遺伝子治療 / Notch
Research Abstract	癌抑制遺伝子p53の機能解明を目的として,次の2つの成果を得た. 1.cDNA-RDA(representational difference analysis)法によりp53欠損マウス由来胎仔線維芽細胞p53(-/-)MEFと正常p53(+/+)MEFで発現量の異なる21種類の遺伝子を同定し,そのうちSCBP1(sodium channel beta induced by p53)に着目し機能解析を行った.SCBP1の発現は,p53強制発現系における発現誘導および正常型p53をもつヒト癌細胞においてもDNA傷害性抗がん剤で誘導されることを確認した.遺伝子上流および第3イントロンに存在するp53応答配列が転写活性化能を有すること,またSCBP1が増殖抑制能を有することを明らかにした.p53が細胞内イオン動態の制御を介して細胞増殖あるいはアポトーシス誘導を行う可能性が示唆された. 2.p53ファミリー遺伝子はp53と高い相同性を有するが,ヒト癌における遺伝子変異の頻度は低く,p53ファミリーメンバーの生体での役割はp53自身とは異なることが予想される.cDNAマイクロアレイ解析によって,Notch受容体のリガンドをコードするJAG1およびJAG2遺伝子がp63およびp73によって特異的に発現上昇することを見つけた.p63遺伝子の機能の少なくとも一部はJAG1/2を介して細胞,組織の分化・発生に深く関与していることを明らかにした.

Research Products
(9 results)

All Other

All Publications (9 results)

[Publications] Morimoto I: "Identification of the osteopontin gene as a direct target of p53"Genes, Chromosomes & Cancer. 33. 270-278 (2002)
[Publications] Sasaki Y: "The p53 family member genes are involved in the Notch signal pathway"J Biol Chem. 277・1. 719-724 (2002)
[Publications] Yamaguchi A: "Detection of human papillomavirus DNA by PCR/microfluorometry for screening of cervical cancer"Clin Chim Acta.. 318・1-2. 41-49 (2002)
[Publications] Kikuchi T: "Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors"Oncogene. 21・17. 2741-2749 (2002)
[Publications] Satoh A: "DNA methylation and histone deacetylation associated with silencing DAP kinase gene expression in colorectal and gastric cancers"British J Cancer. 86. 1817-1823 (2002)
[Publications] Ogi K: "Aberrant methylation of multiple genes and clinicopathological features in oral squamous cell carcinoma"Clinical Cancer Research. 8・10. 3164-3171 (2002)
[Publications] Nishimori H: "The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors"Oncogene. 21. 8302-8309 (2002)
[Publications] Watanabe G: "Induction of tenascin-C by tumor specific EWS-ETS fusion genes"Genes Chromosomes & Cancer. 36・3. 224-232 (2003)
[Publications] Lee G-H: "Analysis of lung tumorigenesis in chimeric mice indicates the pulmonary adenoma resistance 2 (Par2) locus to operate in the tumor-initiation stage in a cell-autonomous manner : detection of polymorphisms in the Poli gene as a candidate for Par2"Oncogene. (in press).

2002 Fiscal Year Annual Research Report

p53とその標的遺伝子群の機能解析

Principal Investigator

時野 隆至 札幌医科大学, 医学部, 教授 (40202197)

Research Products

[Publications] Morimoto I: "Identification of the osteopontin gene as a direct target of p53"Genes, Chromosomes & Cancer. 33. 270-278 (2002)

[Publications] Sasaki Y: "The p53 family member genes are involved in the Notch signal pathway"J Biol Chem. 277・1. 719-724 (2002)

[Publications] Yamaguchi A: "Detection of human papillomavirus DNA by PCR/microfluorometry for screening of cervical cancer"Clin Chim Acta.. 318・1-2. 41-49 (2002)

[Publications] Kikuchi T: "Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors"Oncogene. 21・17. 2741-2749 (2002)

[Publications] Satoh A: "DNA methylation and histone deacetylation associated with silencing DAP kinase gene expression in colorectal and gastric cancers"British J Cancer. 86. 1817-1823 (2002)

[Publications] Ogi K: "Aberrant methylation of multiple genes and clinicopathological features in oral squamous cell carcinoma"Clinical Cancer Research. 8・10. 3164-3171 (2002)

[Publications] Nishimori H: "The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors"Oncogene. 21. 8302-8309 (2002)

[Publications] Watanabe G: "Induction of tenascin-C by tumor specific EWS-ETS fusion genes"Genes Chromosomes & Cancer. 36・3. 224-232 (2003)

[Publications] Lee G-H: "Analysis of lung tumorigenesis in chimeric mice indicates the pulmonary adenoma resistance 2 (Par2) locus to operate in the tumor-initiation stage in a cell-autonomous manner : detection of polymorphisms in the Poli gene as a candidate for Par2"Oncogene. (in press).

時野隆至札幌医科大学, 医学部, 教授 (40202197)