1990 Fiscal Year Annual Research Report

正常造血幹細胞,造血因子と造血器腫瘍との比較と相互関係

Research Project

Project/Area Number	02256106
Research Institution	Research Institute for Clinical Oncology, Saitama Cancer Center
Principal Investigator	穂積本男埼玉県立がんセンター, 研究所, 所長 (50113478)
Co-Investigator(Kenkyū-buntansha)	白川茂三重大学, 医学部, 教授 (20026850) 平井久丸東京大学, 医学部, 講師 (90181130) 斎藤政樹自治医科大学, 医学部, 教授 (60012762) 帯刀益夫東北大学, 抗酸菌病研究所・細胞生物学部, 教授 (10099971) 渡辺利雄東京大学, 応用微生物学研究所, 助手 (60201208)
Keywords	分化誘導因子 / フレンド白血病細胞 / 細胞内分化因子 / cーmyc遺伝子 / ガングリオシド / 受容体遺伝子 / 染色体相互転座 / プロテインキナ-ゼC
Research Abstract	1.マウス骨髄性白血病M1細胞の分化誘導因子(D因子)は、1)各種サイトカインとの併用処理でM1細胞の分化誘導を修飾すること、2)ブタ腎上皮LLCーPK_1細胞の分化を抑制することを明らかにした。また、各種サイトカインはレチノイン酸、ビタミンD_3活性体によるヒト骨髄性白血病細胞の分化誘導と増殖抑制を促進することを見出した(穂積)。2.フレンド白血病細胞の3種類の細胞内分化因子(DIFーI、DIFーII、DIFーIII)の中で、DIFーIIIはDIFーIのリン酸化チロシンのDIFーIIによる脱リン酸化反応によって生成することを明らかにした(渡辺)。3.cーmyc遺伝子によるフレンド白血病細胞の分化誘導抑制機序を解析し、cーmycは分化の決定の過程と分化特異的遺伝子発現の過程とを抑制していることを明らかにした。また、cーmyc蛋白質の機能領域を解析し、癌原性と分化抑制を関与する領域は同一であるが、分化特異的遺伝子発現を抑制する領域とは異なることを明らかにした(帯刀)。4.シアロコレステロ-ルとシアロジグリセリドにヒト前骨髄球性白血病HLー60細胞の分化誘導と増殖抑制効果のあることを見出した。また、分化誘導性ガングリオシドはインシュリン受容体βサブユニットの自己リン酸化反応の特異的な抑制作用を介してHLー60細胞を分化させることを示唆した。(斎藤)。5.造血細胞に特異的に発現し、造血細胞の増殖に関与すると推察される新たなチロシンキナ-ゼ型受容体遺伝子1tkをヒト白血病K562細胞のcDNAライブラリ-から単離し、構造を明らかにした(平井)。6.リンパ球、骨髄球両者の性質を示すヒト白血病細胞は多能性幹細胞に由来し、特定の染色体相互転座発生は細胞の分化と密接に関連していることを明らかにした。また。白血病細胞型および分化段階によってプロティンキナ-ゼC亜型に差違があることを明らかにした(白川)。

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] Tomida,M.: "Inhibition of development of Na^+ーdependent hexose transport in renal epithelial LLCーP_1 cells by differentiation stimulating factor for myeloid leukemic cells" FEBS Letters. 268. 261-264 (1990)
[Publications] Nakamaki,T.: "Difference in effects of interferonーα and interferonーγ on the induction of differentiation of retinoic acidtreated acute myeloid leukemic cells in primary culture" Leukemia Research. 14. 785-794 (1990)
[Publications] OkabeーKado,J.: "Effects of transforming growth factorーβ and activin A on vitamin D_3ーinduced monocytic differentiation of myeloid leukemia cells" Anticancer Research. (1991)
[Publications] Sakashita,A.: "Granulocyte colonyーstimulating factor,not granulocyteーmacrophage colonyーstimulating factor,cooperated with retinoic acid on the induction of functional Nーformylーmethionylphenylalanine receptors on HLー60 cells" Leukemia Research. (1991)
[Publications] Watanabe,T.: "Induction of <in>___ー <vitro>___ー differentiation of mouse erythroleukemia cells by genistein,and inhibitor of tyrosine protein kinases" Cancer Research. 51. (1991)
[Publications] Nemoto,Y.: "Antiーsense RNA expression of a latent period gene (MER5) inhibits the differentiation of murine erythroleukemia cells" Gene. 91. 261-265 (1990)
[Publications] Takada,S.: "Overexpression of cーmyc inhibits the appearance of a specific DNase I hypersensitive site in the βーglobin chromatin in murine erythroleukemia cells" Japanese Journal of Cancer Research. (1991)
[Publications] Saito,M.: "Synthetic sialyl glycolipids(sialoーcholesterol and sialoーdiglyceride)induce granulocytic differentiation of human myelogenous leukemia cell line HLー60" FEBS Letters. 27. 85-88 (1990)
[Publications] Nakamura,M.: "Ganglioside GM3 can induce megakaryocytoid differentiation of human leukemia cell line K562 cells" Cancer Research. (1991)
[Publications] Maru,Y.: "Overexpression confers an oncogenic potential upon the <eph>___ー gene" Oncogene. 5. 445-447 (1990)
[Publications] Maru,Y.: "Human <ltk>___ー:Gene structure and preferential expression in human leukemic cells" Oncogene Research. 5. 199-204 (1990)
[Publications] Ikeda,K.: "Genetic heterogeneity in blast crisis of chronic myelocytic leukemia" Leukemia Research. 14. 195-201 (1990)
[Publications] Ikeda,K.: "Oligoclonal immunoglobulin gene rearrangements in Philadelphiaーchromosome positive common acute lymphoーblastic leukemia" Japanese Journal of Cancer Research. 81. 340-344 (1990)
[Publications] Nishikawa,M.: "Decreased expression of type II protein kinase C in HLー60 variant cells resistant to induction of cell differentiation by phorbol diester" Cancer Research. 50. 621-626 (1990)
[Publications] Kitayama,N.: "A role for calmodulin in the growth of human hematopoietic progenitor cells" Blood. 75. 1446-1454 (1990)
[Publications] Hozumi,M.: "Molecular Control of Haemopoiesis,Ciba Foundation Symposium 148" John Wiley & Sons,Chichester,U.K., 18 (1990)
[Publications] 穂積本男: "白血病の分化誘導療法" 中外医学社,東京, 218 (1990)
[Publications] Oishi,M.: "Mechanism of Differentiation" CRC Press,Boca Raton,Florida,U.S.A., 13 (1990)
[Publications] Watanabe,T.: "The Status of Differentiation Therapy of Cancer" Raven Press,New York,U.S.A., (1991)
[Publications] Saito,M.: "The Status of Differentiation Therapy of Cancer" Raven Press,New York,U.S.A., (1991)
[Publications] Kita,K.: "Lymphoid Malignancy:Immunology and Cytogenetics" Friend & Wood,Philadelphia,U.S.A, 11 (1990)
[Publications] 北堅吉: "日本血液学全書「分子血液学」" 丸善,東京, 9 (1990)

1990 Fiscal Year Annual Research Report

正常造血幹細胞,造血因子と造血器腫瘍との比較と相互関係

Principal Investigator

穂積 本男 埼玉県立がんセンター, 研究所, 所長 (50113478)

Research Products

[Publications] Tomida,M.: "Inhibition of development of Na^+ーdependent hexose transport in renal epithelial LLCーP_1 cells by differentiation stimulating factor for myeloid leukemic cells" FEBS Letters. 268. 261-264 (1990)

[Publications] Nakamaki,T.: "Difference in effects of interferonーα and interferonーγ on the induction of differentiation of retinoic acidtreated acute myeloid leukemic cells in primary culture" Leukemia Research. 14. 785-794 (1990)

[Publications] OkabeーKado,J.: "Effects of transforming growth factorーβ and activin A on vitamin D_3ーinduced monocytic differentiation of myeloid leukemia cells" Anticancer Research. (1991)

[Publications] Sakashita,A.: "Granulocyte colonyーstimulating factor,not granulocyteーmacrophage colonyーstimulating factor,cooperated with retinoic acid on the induction of functional Nーformylーmethionylphenylalanine receptors on HLー60 cells" Leukemia Research. (1991)

[Publications] Watanabe,T.: "Induction of <in>___ー <vitro>___ー differentiation of mouse erythroleukemia cells by genistein,and inhibitor of tyrosine protein kinases" Cancer Research. 51. (1991)

[Publications] Nemoto,Y.: "Antiーsense RNA expression of a latent period gene (MER5) inhibits the differentiation of murine erythroleukemia cells" Gene. 91. 261-265 (1990)

[Publications] Takada,S.: "Overexpression of cーmyc inhibits the appearance of a specific DNase I hypersensitive site in the βーglobin chromatin in murine erythroleukemia cells" Japanese Journal of Cancer Research. (1991)

[Publications] Saito,M.: "Synthetic sialyl glycolipids(sialoーcholesterol and sialoーdiglyceride)induce granulocytic differentiation of human myelogenous leukemia cell line HLー60" FEBS Letters. 27. 85-88 (1990)

[Publications] Nakamura,M.: "Ganglioside GM3 can induce megakaryocytoid differentiation of human leukemia cell line K562 cells" Cancer Research. (1991)

[Publications] Maru,Y.: "Overexpression confers an oncogenic potential upon the <eph>___ー gene" Oncogene. 5. 445-447 (1990)

[Publications] Maru,Y.: "Human <ltk>___ー:Gene structure and preferential expression in human leukemic cells" Oncogene Research. 5. 199-204 (1990)

[Publications] Ikeda,K.: "Genetic heterogeneity in blast crisis of chronic myelocytic leukemia" Leukemia Research. 14. 195-201 (1990)

[Publications] Ikeda,K.: "Oligoclonal immunoglobulin gene rearrangements in Philadelphiaーchromosome positive common acute lymphoーblastic leukemia" Japanese Journal of Cancer Research. 81. 340-344 (1990)

[Publications] Nishikawa,M.: "Decreased expression of type II protein kinase C in HLー60 variant cells resistant to induction of cell differentiation by phorbol diester" Cancer Research. 50. 621-626 (1990)

[Publications] Kitayama,N.: "A role for calmodulin in the growth of human hematopoietic progenitor cells" Blood. 75. 1446-1454 (1990)

[Publications] Hozumi,M.: "Molecular Control of Haemopoiesis,Ciba Foundation Symposium 148" John Wiley & Sons,Chichester,U.K., 18 (1990)

[Publications] 穂積 本男: "白血病の分化誘導療法" 中外医学社,東京, 218 (1990)

[Publications] Oishi,M.: "Mechanism of Differentiation" CRC Press,Boca Raton,Florida,U.S.A., 13 (1990)

[Publications] Watanabe,T.: "The Status of Differentiation Therapy of Cancer" Raven Press,New York,U.S.A., (1991)

[Publications] Saito,M.: "The Status of Differentiation Therapy of Cancer" Raven Press,New York,U.S.A., (1991)

[Publications] Kita,K.: "Lymphoid Malignancy:Immunology and Cytogenetics" Friend & Wood,Philadelphia,U.S.A, 11 (1990)

[Publications] 北 堅吉: "日本血液学全書「分子血液学」" 丸善,東京, 9 (1990)

穂積本男埼玉県立がんセンター, 研究所, 所長 (50113478)

[Publications] Watanabe,T.: "Induction of <in>_ー <vitro>_ー differentiation of mouse erythroleukemia cells by genistein,and inhibitor of tyrosine protein kinases" Cancer Research. 51. (1991)

[Publications] 穂積本男: "白血病の分化誘導療法" 中外医学社,東京, 218 (1990)

[Publications] 北堅吉: "日本血液学全書「分子血液学」" 丸善,東京, 9 (1990)