2000 Fiscal Year Annual Research Report

リンパ系腫瘍に関わる新規癌抑制遺伝子の単離

Research Project

Project/Area Number	11670990
Research Institution	Nagoya University
Principal Investigator	木下朝博名古屋大学, 医学部, 助手 (60283446)
Co-Investigator(Kenkyū-buntansha)	永井宏和名古屋大学, 医学部, 医員村手隆名古屋大学, 医学部, 教授 (30239537)
Keywords	悪性リンパ腫 / 癌抑制遺伝子 / 染色体 / 6p / 1q / PROX1 / DNAメチル化
Research Abstract	我々はこれまでの解析によって悪性リンパ腫で染色体1番長腕と6番短腕に高頻度の欠失領域が存在する事を見出した。これらは癌抑制遺伝子が存在する候補領域と考えられる。ホメオボックス遺伝子PROX1は我々が見いだした染色体1番長腕の候補領域に存在する。今回癌抑制遺伝子としての可能性を検討するために、造血器腫瘍におけるPROX1遺伝子の発現、構造異常、メチル化による遺伝子の不活化について検討した。 RT-PCR法による解析では検討した29種類の造血系細胞株では一部の細胞株で著しい発現の低下を認めた。一方正常の造血組織では全組織で発現が認められた。 RT-PCRにてPROX1の発現が認められなかったRaji細胞を5-aza-2'-deoxycytidineで処理したところその発現が回復し、発現低下にDNAメチル化が関与することが示唆された。造血器腫瘍由来細胞株11種類、非特異的リンパ節炎2例、健康人の末梢血単核球3症例、正常脾臓細胞の計17種類のDNAを用いintron 1のDNAメチル化をbisulfite mapping法で検討したところ、DNAメチル化の亢進は造血器腫瘍由来細胞株のみに認められ、発現とメチル化に強い相関を認めた。さらにPCR-SSCP法にて遺伝子変異をスクリーニングしたところ、5種類の細胞株(BALL1,HEL,THP6,RPMI8402,Jurkat)にてmissenseおよびnonsense mutationが認められた。以上造血器系の細胞株でPROX1の発現消失が認められ、そのmRNAの発現とDNAメチル化の相関が認められた。また細胞株にてmissense及びnonsense mutationが認められた。これらの結果よりPROX1は癌抑制遺伝子の候補になりうると考えられ、現在その機能について細胞増殖への関与などを検討中である。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] H.Suzuki: "Clonality analysis of refractory anemia with ring sideroblasts : simultaneous study of clonality and cytochemistry of bone marrow progenitors.."Leukemia. 13. 130-134 (1999)
[Publications] H.Nagai: "Identification and Mapping of Novel Tumor Suppressor Loci on 6p in Diffuse Large B-cell non-Hodgkin Lymphoma.."Genes, Chromosomes & Cancer. 25. 277-283 (1999)
[Publications] Y.Nakahara: "Clonality analysis of granulocytes and T lumphocytes in healthy females by the PCR-based HUMARA method.."Int.J.Hematol.. 69. 237-243 (1999)
[Publications] H.Kosugi: "Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia : a new approach to anti-leukemia therapy."Leukemia. 13. 1316-1324 (1999)
[Publications] A.Tomita: "c-Myb acetylation at the carboxyl-terminally conserved domain by transcriptional co-activator p300."Oncogene. 19. 444-451 (2000)
[Publications] T.Uchida: "Clonality analysis by methylation-specific PCR for the human androgen-receptor gene (HUMARA-MSP)."Leukemia. 14. 207-212 (2000)
[Publications] E.Aoki: "Methylation status of the p15INK4B gene in hematopoietic progenitors and peripheral blood cells in myelodysplastic syndromes."Leukemia. 14. 586-593 (2000)
[Publications] S.Sasaki: "Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15."Oncogene. 19. 3739-3749 (2000)
[Publications] M.Yuge: "HSNF5/INI1 genen mutations in lymphoid malignancy."Cancer Genet Cytogenet. 122. 37-42 (2000)
[Publications] T Uchida: "Hypermethylation of p16INK4A gene promoter during the progression of plasma cell dyscrasia."Leukemia. 15. 157-165 (2001)
[Publications] H Ohashi: "Relationship between methylation of the p15 gene and actopic expression of the EVI-1 gene in myelodysplastic syndromes (MDS)."Leukemia. 19(in press). (2001)

2000 Fiscal Year Annual Research Report

リンパ系腫瘍に関わる新規癌抑制遺伝子の単離

Principal Investigator

木下 朝博 名古屋大学, 医学部, 助手 (60283446)

Research Products

[Publications] H.Suzuki: "Clonality analysis of refractory anemia with ring sideroblasts : simultaneous study of clonality and cytochemistry of bone marrow progenitors.."Leukemia. 13. 130-134 (1999)

[Publications] H.Nagai: "Identification and Mapping of Novel Tumor Suppressor Loci on 6p in Diffuse Large B-cell non-Hodgkin Lymphoma.."Genes, Chromosomes & Cancer. 25. 277-283 (1999)

[Publications] Y.Nakahara: "Clonality analysis of granulocytes and T lumphocytes in healthy females by the PCR-based HUMARA method.."Int.J.Hematol.. 69. 237-243 (1999)

[Publications] H.Kosugi: "Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia : a new approach to anti-leukemia therapy."Leukemia. 13. 1316-1324 (1999)

[Publications] A.Tomita: "c-Myb acetylation at the carboxyl-terminally conserved domain by transcriptional co-activator p300."Oncogene. 19. 444-451 (2000)

[Publications] T.Uchida: "Clonality analysis by methylation-specific PCR for the human androgen-receptor gene (HUMARA-MSP)."Leukemia. 14. 207-212 (2000)

[Publications] E.Aoki: "Methylation status of the p15INK4B gene in hematopoietic progenitors and peripheral blood cells in myelodysplastic syndromes."Leukemia. 14. 586-593 (2000)

[Publications] S.Sasaki: "Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15."Oncogene. 19. 3739-3749 (2000)

[Publications] M.Yuge: "HSNF5/INI1 genen mutations in lymphoid malignancy."Cancer Genet Cytogenet. 122. 37-42 (2000)

[Publications] T Uchida: "Hypermethylation of p16INK4A gene promoter during the progression of plasma cell dyscrasia."Leukemia. 15. 157-165 (2001)

[Publications] H Ohashi: "Relationship between methylation of the p15 gene and actopic expression of the EVI-1 gene in myelodysplastic syndromes (MDS)."Leukemia. 19(in press). (2001)

木下朝博名古屋大学, 医学部, 助手 (60283446)