2000 Fiscal Year Annual Research Report

足場非依存的増殖及び細胞周期進行におけるCD98役割の解析

Research Project

Project/Area Number	12215009
Research Institution	Kinki University
Principal Investigator	益子高近畿大学, 薬学部, 教授 (30157200)
Co-Investigator(Kenkyū-buntansha)	関政幸東北大学, 大学院・薬学研究科, 講師 (70202140)
Keywords	CD98 / CD98hc / CD98lc / 足場非依存的増殖 / 細胞悪性化 / アミノ酸輸送
Research Abstract	全長、断片化(CD98hc細胞外領域の約半分または3/4を欠失)および変異導入(CD98lcとの結合に必要なN末端から103または325番目のシステインを個別にまたは両方セリンに変換)したヒトまたはラットCD98hc cDNAをNIH3T3とBALB3T3に導入、遺伝子トランスフェクタントを樹立した。これらのトランスフェクタントの性状を解析した結果、1)CD98hcの過剰発現により細胞悪性化が引き起こされること、2)細胞悪性化には導入CD98hcと内在性CD98lcとのジスルフィド結合による会合が必須であること、3)CD98hc細胞外領域の欠失により細胞悪性化が増強すること、が明らかとなった。 CD98hc遺伝子導入によりマウス線維芽細胞の足場非依存的増殖能の獲得を始めとする形質転換が起こり、CD98hcの癌遺伝子としての性質が浮き彫りとなった。この活性はCD98hc細胞外領域の欠失により増強したため、細胞悪性化が細胞外領域により制御されていることも明らかとなった。また、CD98hc過剰発現による細胞悪性化にはCD98lcとの結合が必須であることも証明されたため、今後、CD98lcのアミノ酸輸送活性とCD98hcの細胞悪性化活性との関わりを解明することが重要な課題である。

Research Products

(8 results)

All Other

All Publications (8 results)

[Publications] Onoda,F,: "Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae"Mol.Gen.Genet.. 264. 702-708 (2001)
[Publications] Hara,K.: "Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain"Oncogene. 19. 6209-6215 (2000)
[Publications] Wang,W.: "Possible association of BLM in decreasing DNA double strand breaks during DNA replication"EMBO J.. 19. 3428-3435 (2000)
[Publications] Kawabe,Y,: "Covalent modification of the Werner's syndrome gene product with the ubiquitin-related protein, SUMO-1"J.Biol.Chem.. 275. 20963-20966 (2000)
[Publications] Kawabe,T,: "Differential regulation of human RecQ family helicases in cell transformation and cell cycle"Oncogene. 19. 4764-4772 (2000)
[Publications] Onoda,F,: "Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene"Mutat.Res.. 459. 203-209 (2000)
[Publications] Shishido,T.: "Colocalization of GP125/CD98 with tropomyosin isoforms at the cell-cell adhesion boundary"J.Biochem.. 127. 354-361 (2000)
[Publications] Shishido,T.: "Transformation of Balb3T3 cells caused by over-expression of rat CD98 heavy chain (hc) requires its association with light chain : Mis-sense mutation in a cysteine residue of CD98hc eliminates its transforming activity"Int.J.Cancer. 87. 311-316 (2000)

2000 Fiscal Year Annual Research Report

足場非依存的増殖及び細胞周期進行におけるCD98役割の解析

Principal Investigator

益子 高 近畿大学, 薬学部, 教授 (30157200)

Research Products

[Publications] Onoda,F,: "Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae"Mol.Gen.Genet.. 264. 702-708 (2001)

[Publications] Hara,K.: "Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain"Oncogene. 19. 6209-6215 (2000)

[Publications] Wang,W.: "Possible association of BLM in decreasing DNA double strand breaks during DNA replication"EMBO J.. 19. 3428-3435 (2000)

[Publications] Kawabe,Y,: "Covalent modification of the Werner's syndrome gene product with the ubiquitin-related protein, SUMO-1"J.Biol.Chem.. 275. 20963-20966 (2000)

[Publications] Kawabe,T,: "Differential regulation of human RecQ family helicases in cell transformation and cell cycle"Oncogene. 19. 4764-4772 (2000)

[Publications] Onoda,F,: "Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene"Mutat.Res.. 459. 203-209 (2000)

[Publications] Shishido,T.: "Colocalization of GP125/CD98 with tropomyosin isoforms at the cell-cell adhesion boundary"J.Biochem.. 127. 354-361 (2000)

[Publications] Shishido,T.: "Transformation of Balb3T3 cells caused by over-expression of rat CD98 heavy chain (hc) requires its association with light chain : Mis-sense mutation in a cysteine residue of CD98hc eliminates its transforming activity"Int.J.Cancer. 87. 311-316 (2000)

益子高近畿大学, 薬学部, 教授 (30157200)