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

Genetic inactivation of ApoJ/clusterin: effects on prostate tumourigenesis and metastatic spread / S., Bettuzzi; Davalli, Pierpaola; S., Davoli; O., Chayka; F., Rizzi; L., Belloni; Pellacani, Davide; Fregni, Giulia; Astancolle, Serenella; M., Fassan; Corti, Arnaldo; R., Baffa; A., Sala. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 28:49(2009), pp. 4344-4352. [10.1038/onc.2009.286]

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

DAVALLI, Pierpaola;PELLACANI, Davide;FREGNI, GIULIA;ASTANCOLLE, Serenella;CORTI, Arnaldo;
2009

Abstract

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
2009
28
49
4344
4352
Genetic inactivation of ApoJ/clusterin: effects on prostate tumourigenesis and metastatic spread / S., Bettuzzi; Davalli, Pierpaola; S., Davoli; O., Chayka; F., Rizzi; L., Belloni; Pellacani, Davide; Fregni, Giulia; Astancolle, Serenella; M., Fassan; Corti, Arnaldo; R., Baffa; A., Sala. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 28:49(2009), pp. 4344-4352. [10.1038/onc.2009.286]
S., Bettuzzi; Davalli, Pierpaola; S., Davoli; O., Chayka; F., Rizzi; L., Belloni; Pellacani, Davide; Fregni, Giulia; Astancolle, Serenella; M., Fassan...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/624603
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