1995 Fiscal Year Annual Research Report

がん関連遺伝子の個体レベルでの機能解析

Research Project

Project/Area Number	06283231
Research Institution	Kumamoto University
Principal Investigator	相沢慎一熊本大学, 医学部, 教授 (60073011)
Keywords	FAK / mos / 相同組換え / ES細胞 / 中胚葉 / 細胞運動 / lanellipodia / microspikes
Research Abstract	1・胚性未分化細胞での相同組換えによりFAK欠損マウスを作製し、FAKが細胞-細胞外マトリックス相互作用に果たす役割について解析した。FAK欠損胚性未分化細胞は、in vitro,in vivoで三胚葉由来の各種細胞に分化し、分化能の欠損は認められなかった。FAK欠損胚は着床し轟胚形成を開始するが、胚発生8日目前後に異常胚となり発生を停止した。異常は中胚葉に特徴的で、その欠乏によると想定された。しかし中胚葉の各種細胞の分化は認められ、各種分化マーカーの発現を調べたところ、中胚葉細胞の分化能自体の欠損は認められなかった。そこで細胞を培養し、細胞の運動能を計測したところ、運動速度が約半分に低下し、かつpolarな運動形態を示さず、non-polarな形態のまま移動することが明らかとなった。そこで細胞骨格系、細部-基質接着点の異常を調べたところ、弱いclose contactの形成は起こるがfocal adhesionの形成が起こらず、この為細胞は正常細胞で認められる移動方向のみならず、全ての方向にlamellipodia,ruffles,microspikesを出した状態に留まっていることが明らかとなった。この状態はv-Srcによる細胞癌化に際しての細胞変化と類似し、v-SrcによるFAKリン酸化の高進は、FAK不活性化である可能性を示唆した。 2・先にc-mos欠損マウスを作製し、mosは成熟未受精卵をMII期に安定に停止し、単為発生抑制に働いていることを明らかにした。単為発生は卵巣腫瘍の発症に密接な関連があり、実際c-mos欠損マウスでは卵巣テラトーマが高発する。ヒト卵巣腫瘍のモデルとして卵巣腫瘍発症に至る過程を明らかにした。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] J.A.Gross,: "Control of lymphogenesis by p50csk,a regulatory protein tyrosine kinase." J.Exp.Med.181. 463-473 (1995)
[Publications] L.Hu,: "P53 controls proliferation of early B lineage cells by a p21 (WAF1/CIP1) -independent pathway." Biochem.Biophys.Res.Commun.206. 948-954 (1995)
[Publications] K.Sakimura,: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor el subunit." Nature. 373. 151-155 (1995)
[Publications] S.Aizawa,: "Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells." Biochem.Biophys.Res.Commun.209. 300-309 (1995)
[Publications] K.Tobe,: "Identification of a 190-kDa protein as a novel substrate for the insulin receptor kinase functionally similar to insulin receptor substrate-1." J.Biol.Chem.270. 5698-5701 (1995)
[Publications] M.Yoshida,: "A new strategy of gene-trapping in ES cells using 3'RACE" Transgenic Research.4. 277-287 (1995)
[Publications] N.Kashiwabuchi,: "Impairment of motor coordination,Purkinje cell synapse formation and cerebellar long-term depression in GluRd2 mutant mice." Cell. 81. 245-252 (1995)
[Publications] Y.Fruta,: "Ovarian teratomas. in mice lacking the protooncogene,c-Mos." Jpn.J.Cancer Res.86. 540-545 (1995)
[Publications] K.Ikeda,: "Reduced spontaneous activity of mice defective in the e4 subunit of the NMDA receptor channel." Mol.Brain Res.33. 61-71 (1995)
[Publications] D.Ilic,: "FAK-deficiency causes mesodermal defects by diminished cell mobility with enhanced focal adhesion formation." Nature. 377. 539-544 (1995)
[Publications] I.Matsuo,: "Mouse Otx2 functions in the patterning of rostral head" Genes & Dev.9. 2646-2658 (1995)
[Publications] T.Tamura,: "An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes." Nature. 376. 596-599 (1995)
[Publications] S.Kanazawa,: "Integrin-stimulation decreases tyrosine phosphorylation and activity of focal adhesion kinase in thymocytes" Biophys.Biochem Res.Commun.215. 438-445 (1995)
[Publications] Y.Fruta,: "Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase FAK" Oncogene. 11. 1989-1995 (1995)
[Publications] S.Kuratani,: "Patterning of the cranial nerve in the chick embryo is dependent on cranial mesoderm and rhombomeric metamerism" Devel.Growth & Diff.37. 717-731 (1995)
[Publications] Y.Shigetani,: "Overlapping origins of pharyngeal arch crest cells on the postotic hindbrain." Devel.Growth & Diff.37. 733-746 (1995)
[Publications] T.Sakai: "Tenascin-C inductionby the diffusible factor epidermal growth factor in stroma-epithelial interactions." J.Cell.Physiol.165. 18-29 (1995)
[Publications] Y.Enokido,: "p53 involves cytosine arabinoside-induced apoptosis in cultured cerebellar granule neurons" Neuroscience Letters. 203. 1-4 (1995)
[Publications] M.Shimoji,: "Establishment of immoratal hepatocytes from a CYP3A7-transgenic/p53-knockout mouse." Biochem.Biophys.Res.Commun.217. 1001-1005 (1995)

1995 Fiscal Year Annual Research Report

がん関連遺伝子の個体レベルでの機能解析

Principal Investigator

相沢 慎一 熊本大学, 医学部, 教授 (60073011)

Research Products

[Publications] J.A.Gross,: "Control of lymphogenesis by p50csk,a regulatory protein tyrosine kinase." J.Exp.Med.181. 463-473 (1995)

[Publications] L.Hu,: "P53 controls proliferation of early B lineage cells by a p21 (WAF1/CIP1) -independent pathway." Biochem.Biophys.Res.Commun.206. 948-954 (1995)

[Publications] K.Sakimura,: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor el subunit." Nature. 373. 151-155 (1995)

[Publications] S.Aizawa,: "Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells." Biochem.Biophys.Res.Commun.209. 300-309 (1995)

[Publications] K.Tobe,: "Identification of a 190-kDa protein as a novel substrate for the insulin receptor kinase functionally similar to insulin receptor substrate-1." J.Biol.Chem.270. 5698-5701 (1995)

[Publications] M.Yoshida,: "A new strategy of gene-trapping in ES cells using 3'RACE" Transgenic Research.4. 277-287 (1995)

[Publications] N.Kashiwabuchi,: "Impairment of motor coordination,Purkinje cell synapse formation and cerebellar long-term depression in GluRd2 mutant mice." Cell. 81. 245-252 (1995)

[Publications] Y.Fruta,: "Ovarian teratomas. in mice lacking the protooncogene,c-Mos." Jpn.J.Cancer Res.86. 540-545 (1995)

[Publications] K.Ikeda,: "Reduced spontaneous activity of mice defective in the e4 subunit of the NMDA receptor channel." Mol.Brain Res.33. 61-71 (1995)

[Publications] D.Ilic,: "FAK-deficiency causes mesodermal defects by diminished cell mobility with enhanced focal adhesion formation." Nature. 377. 539-544 (1995)

[Publications] I.Matsuo,: "Mouse Otx2 functions in the patterning of rostral head" Genes & Dev.9. 2646-2658 (1995)

[Publications] T.Tamura,: "An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes." Nature. 376. 596-599 (1995)

[Publications] S.Kanazawa,: "Integrin-stimulation decreases tyrosine phosphorylation and activity of focal adhesion kinase in thymocytes" Biophys.Biochem Res.Commun.215. 438-445 (1995)

[Publications] Y.Fruta,: "Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase FAK" Oncogene. 11. 1989-1995 (1995)

[Publications] S.Kuratani,: "Patterning of the cranial nerve in the chick embryo is dependent on cranial mesoderm and rhombomeric metamerism" Devel.Growth & Diff.37. 717-731 (1995)

[Publications] Y.Shigetani,: "Overlapping origins of pharyngeal arch crest cells on the postotic hindbrain." Devel.Growth & Diff.37. 733-746 (1995)

[Publications] T.Sakai: "Tenascin-C inductionby the diffusible factor epidermal growth factor in stroma-epithelial interactions." J.Cell.Physiol.165. 18-29 (1995)

[Publications] Y.Enokido,: "p53 involves cytosine arabinoside-induced apoptosis in cultured cerebellar granule neurons" Neuroscience Letters. 203. 1-4 (1995)

[Publications] M.Shimoji,: "Establishment of immoratal hepatocytes from a CYP3A7-transgenic/p53-knockout mouse." Biochem.Biophys.Res.Commun.217. 1001-1005 (1995)

相沢慎一熊本大学, 医学部, 教授 (60073011)