1995 Fiscal Year Annual Research Report

疾患モデル動物からの未知の病因遺伝子の探求-遺伝性腎癌ラットの病因遺伝子の単離、同定-

Research Project

Project/Area Number	06454719
Research Institution	Cancer Institute
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)	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 ratの発癌機構を解明すべくpositional cloning法によって原因遺伝子の単離、同定をめざした。ついに我々は、Tsc2遺伝子にレトロトランスポゾン挿入によるgermline mutationを見い出しEker rat発見40年目にして原因遺伝子の同定に成功した。ここにEker ratは、現在全く不明である、多彩な症状を示すヒト結節性硬化症(最近、5800人に1人の出生率との報告があり比較的頻度の高い難病)の発症機序解明及び治療、予防の開発の疾患モデルとして、新しい展開を迎えることとなった。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。本研究において我々は、Eker(Tsc2)遺伝子は癌抑制遺伝子であることを証明した。またEker(Tsc2)遺伝子の機能として転写活性能を見い出した。現在、「Eker ratの腎癌の本態はEker(Tsc2)遺伝子不活性化による遺伝子発現制御の異常にある」との作業仮説を立てtarget遺伝子の単離を進めている。我々の最終目的は、疾患モデルからヒト疾患の診断、予防、治療に資する知見を得ようとするものである。

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

疾患モデル動物からの未知の病因遺伝子の探求-遺伝性腎癌ラットの病因遺伝子の単離、同定-

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)