The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNA-binding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNA-damaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68(GSG) protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.

Busà, R., Paronetto, M., Farini, D., Pierantozzi, E., Botti, F., Angelini, D., et al. (2007). The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells. ONCOGENE, 26(30), 4372-4382 [10.1038/sj.onc.1210224].

The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells

FARINI, DONATELLA;BOTTI, FLAVIA;VESPASIANI, GIUSEPPE;SETTE, CLAUDIO
2007-06-28

Abstract

The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNA-binding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNA-damaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68(GSG) protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.
28-giu-2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/17 - ISTOLOGIA
English
Con Impact Factor ISI
Apoptosis; DNA-Binding Proteins; Humans; Aged; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Adaptor Proteins, Signal Transducing; RNA-Binding Proteins; Middle Aged; Prostatic Neoplasms; Male
Busà, R., Paronetto, M., Farini, D., Pierantozzi, E., Botti, F., Angelini, D., et al. (2007). The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells. ONCOGENE, 26(30), 4372-4382 [10.1038/sj.onc.1210224].
Busà, R; Paronetto, M; Farini, D; Pierantozzi, E; Botti, F; Angelini, D; Attisani, F; Vespasiani, G; Sette, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/44609
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