Genetic inactivation of ApoJ/clusterin: effects on prostate tumourigenesis and metastatic spread

被引：37

作者：

Bettuzzi, S. ^{[1
]}

Davalli, P. ^{[2
]}

Davoli, S. ^{[1
]}

Chayka, O. ^{[3
]}

Rizzi, F. ^{[1
]}

Belloni, L. ^{[1
]}

Pellacani, D. ^{[2
]}

Fregni, G. ^{[2
]}

Astancolle, S. ^{[2
]}

Fassan, M. ^{[4
]}

Corti, A. ^{[2
]}

Baffa, R. ^{[4
,5
]}

Sala, A. ^{[3
]}

机构：

[1] Univ Parma, Dept Expt Med, I-43100 Parma, Italy

[2] Univ Modena & Reggio Emilia, Dept Biomed Sci, Modena, Italy

[3] Inst Child Hlth, Mol Haematol & Canc Biol Unit, London, England

[4] Thomas Jefferson Univ, Dept Urol, Philadelphia, PA 19107 USA

[5] MedImmune LLC, Res, Gaithersburg, MD USA

来源：

ONCOGENE | 2009年 / 28卷 / 49期

关键词：

immunohistochemistry; tumour suppressor gene; cell cycle; NF-kappa B; NF-KAPPA-B; TRANSGENIC MOUSE MODEL; EPITHELIAL-CELLS; CANCER CELLS; CLUSTERIN; EXPRESSION; PROGRESSION; INDUCTION; APOPTOSIS; ACTIVATION;

D O I：

10.1038/onc.2009.286

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ApoJ/Clusterin (CLU) is a heterodimeric protein localized in the nucleus, cytoplasm or secretory organelles and involved in cell survival and neoplastic transformation. Its function in human cancer is still highly controversial. In this study, we examined the prostate of mice in which CLU has been genetically inactivated. Surprisingly, we observed transformation of the prostate epithelium in the majority of CLU knockout mice. Either PIN (prostate intraepithelial neoplasia) or differentiated carcinoma was observed in 100 and 87% of mice with homozygous or heterozygous deletion of CLU, respectively. Crossing CLU knockout with TRAMP (prostate cancer prone) mice results in a strong enhancement of metastatic spread. Finally, CLU depletion causes tumourigenesis in female TRAMP mice, which are normally cancer free. Mechanistically, deletion of CLU induces activation of nuclear factor-kB, a potentially oncogenic transcription factor important for the proliferation and survival of prostate cells. Oncogene (2009) 28, 4344-4352; doi: 10.1038/onc.2009.286; published online 28 September 2009

引用

页码：4344 / 4352

页数：9

共 38 条

[1] IDENTIFICATION OF AN ANDROGEN-REPRESSED MESSENGER-RNA IN RAT VENTRAL PROSTATE AS CODING FOR SULFATED GLYCOPROTEIN-2 BY CDNA CLONING AND SEQUENCE-ANALYSIS [J].