drs癌抑制遺伝子による癌化抑制機構（第8回基礎・臨床融合の学内共同研究発表会）（抄録）

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タイトル別名
  • Function of tumor suppressor gene, drs
  • drs ガン ヨクセイ イデンシ ニ ヨル ガンカ ヨクセイ キコウ （ダイ 8カイ キソ リンショウ ユウゴウ ノ ガクナイ キョウドウ ケンキュウ ハッピョウカイ）（ショウロク）

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抄録

type:Departmental Bulletin Paper

The drs gene was originally isolated as a suppressor of v-src transformation. Expression of drs mRNA ismarkedly downregulated in a variety of human cancer cell lines and tissues. Ectopic expression of the Drs protein inducedapoptosis in human cancer cell lines via the novel pathway initiated from the endoplasmic reticulum (ER), involving thebinding to ASY, apoptosis-inducing proteins localized in ER, and activation of caspase-12, -9, and -3. We generated drsknockout (KO) mice and showed that malignant tumors including lymphomas, lung adenocarcinomas and hepatomas weregenerated in about 30% of drs KO mice. These results indicate that drs contributes to the suppression of malignant tumorformation, and this suppression is closely correlated with drs-mediated apoptosis. We also investigated the physiological rolesof drs gene by using mouse embryonic fibroblast (MEF) cells derived from drs KO mice, and found that drs is associated withRab24, autophagy regulating protein, and regulates autophagy maturation under low serum culture conditions. Furthermore,drs suppresses viral replication via mTOR-dependent pathway. These results suggest that drs is involved in the protectiveresponses of the cells against the carcinogenesis and viral infection.

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