1995 Fiscal Year Annual Research Report

遺伝性腎癌ラットの発癌機構の解明

Research Project

Project/Area Number	07272241
Research Institution	Japanese Foundation For Cancer Research
Principal Investigator	樋野興夫財団法人癌研究會, 癌研究所・実験病理部, 部長 (90127910)
Co-Investigator(Kenkyū-buntansha)	土屋晴生財団法人癌研究會, 癌研究所・実験病理部, 研究員 (80260074) 小林敏之財団法人癌研究會, 癌研究所・実験病理部, 研究員 (40260070)
Keywords	遺伝性癌 / 疾患モデル / 腎発癌 / TSC2遺伝子 / ヒト結節性硬化症 / 癌抑制遺伝子
Research Abstract	我々は、Ekerラットの発癌機構の解明を目的としてまずEker (Tsc2) 遺伝子の全構造の決定と機能解析を行った。ラットTsc2遺伝子のgenomicDNAのsizeは約35Kbであり、cording exonは41個もあった。ラットTsc2産物はヒトTSC2産物と全長にわたって約92%の高い相同性を示すことを見い出した。興味あることに、Alternative splicingがexons25and31に見られた。Eker mutationはintron30へのretrotransposon挿入による。さらに、non-cording exonの存在も見い出している (投稿準備中)。exon-intronの構造解析を行い全遺伝子をカバーするPCR-SSCP法のprimerを多数作成しLoss of heterozygosity (LOH) の見られない症例ではintragenic mutationを見い出した。これは、Knudson's two-hitsを証明するものである。また野生型Tsc2遺伝子をEker rat腎癌細胞に導入し増殖が抑えられることを見い出しEker (Tsc2) 遺伝子は癌抑制遺伝子であることを証明した。さらにTsc2遺伝子は転写活性化ドメインを有することを見い出した。また抗体を作成し細胞内局在に関して興味ある知見を得た。我々は、発癌の系統差も確認している。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Kobayashi,T.: "A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer." Nature Genet.9. 70-75 (1995)
[Publications] Kubo,Y.: "Early detection of Knudson's two-hits in preneoplastic renal cells of the Eker rat model by the Laser microdissection procedure." Cancer Res.55. 989-990 (1995)
[Publications] Hino,O.: "The Eker rat,a model of dominantly inherited cancer syndrome." Transplantation Proceed.27. 1529-1531 (1995)
[Publications] Kobayashi,T.: "Isolation of microdissection clones from rat chromosome 10." Mammalian Genome. 6. 216-218 (1995)
[Publications] Hino,O.: "An animal model for tuberous sclerosis (TSC2) in the Eker rat." Rat Genome. 1. 14 (1995)
[Publications] Kubo,Y.: "Alleic loss at the tuberous sclerosis (Tsc2) gene locus in spontaneous uterine leiomyosarcomas and pituitary adenomas in the Eker rat model." Jap.J.Cancer Res.86. 828-832 (1995)
[Publications] Kikuchi,Y.: "Cloning of the rat homologue of the von Hippel-Lindau (VHL) tumor suppressor gene and its non-somatic mutation in rat renal cell carcinomas." Jap.J.Cancer Res.86. 905-909 (1995)
[Publications] Kobayashi,T.: "cDNA structure,alternative splicing and exon-intron organization of the predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model." Nucleic Acids Res.23. 2608-2613 (1995)
[Publications] Kobayashi,T.: "The structure of the rat tuberous sclerosis (Tsc2) gene." Rat Genome.2. 6-10 (1995)
[Publications] Hino,O.: "Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis (TSC2)." Molecular Carcinogenesis. 14. 23-27 (1995)
[Publications] Hino,O.: "Renal carcinogenesis in the Eker rat." J.Cancer Res.and Clinical Oncology.121. 602-605 (1995)
[Publications] Tsuchiya,H.: "Presence of potent transcriptional activation domains in the predisposing tuberous sclerosis (Tsc2) gene product of the Eker rat model." Cancer Res.56. 429-433 (1996)
[Publications] Orimoto,K.: "Suppression of the neoplastic phenotype by replacement of the Tsc2 gene in Eker rat renal carcinoma cells." Biochem.Biophys.Res Commun.(in press.).
[Publications] Hino,O.: "Usefulness of rat cDNA clones in genetic mapping." Rat Genome. (in press.).

1995 Fiscal Year Annual Research Report

遺伝性腎癌ラットの発癌機構の解明

Principal Investigator

樋野 興夫 財団法人癌研究會, 癌研究所・実験病理部, 部長 (90127910)

Research Products

[Publications] Kobayashi,T.: "A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer." Nature Genet.9. 70-75 (1995)

[Publications] Kubo,Y.: "Early detection of Knudson's two-hits in preneoplastic renal cells of the Eker rat model by the Laser microdissection procedure." Cancer Res.55. 989-990 (1995)

[Publications] Hino,O.: "The Eker rat,a model of dominantly inherited cancer syndrome." Transplantation Proceed.27. 1529-1531 (1995)

[Publications] Kobayashi,T.: "Isolation of microdissection clones from rat chromosome 10." Mammalian Genome. 6. 216-218 (1995)

[Publications] Hino,O.: "An animal model for tuberous sclerosis (TSC2) in the Eker rat." Rat Genome. 1. 14 (1995)

[Publications] Kubo,Y.: "Alleic loss at the tuberous sclerosis (Tsc2) gene locus in spontaneous uterine leiomyosarcomas and pituitary adenomas in the Eker rat model." Jap.J.Cancer Res.86. 828-832 (1995)

[Publications] Kikuchi,Y.: "Cloning of the rat homologue of the von Hippel-Lindau (VHL) tumor suppressor gene and its non-somatic mutation in rat renal cell carcinomas." Jap.J.Cancer Res.86. 905-909 (1995)

[Publications] Kobayashi,T.: "cDNA structure,alternative splicing and exon-intron organization of the predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model." Nucleic Acids Res.23. 2608-2613 (1995)

[Publications] Kobayashi,T.: "The structure of the rat tuberous sclerosis (Tsc2) gene." Rat Genome.2. 6-10 (1995)

[Publications] Hino,O.: "Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis (TSC2)." Molecular Carcinogenesis. 14. 23-27 (1995)

[Publications] Hino,O.: "Renal carcinogenesis in the Eker rat." J.Cancer Res.and Clinical Oncology.121. 602-605 (1995)

[Publications] Tsuchiya,H.: "Presence of potent transcriptional activation domains in the predisposing tuberous sclerosis (Tsc2) gene product of the Eker rat model." Cancer Res.56. 429-433 (1996)

[Publications] Orimoto,K.: "Suppression of the neoplastic phenotype by replacement of the Tsc2 gene in Eker rat renal carcinoma cells." Biochem.Biophys.Res Commun.(in press.).

[Publications] Hino,O.: "Usefulness of rat cDNA clones in genetic mapping." Rat Genome. (in press.).

樋野興夫財団法人癌研究會, 癌研究所・実験病理部, 部長 (90127910)