Abstract
BACKGROUND. In prostate cancer, mutations of the phosphatase PTEN can activate the kinase cascade PI3K/Akt/mTOR which induces drug resistance. METHODS. Chemosensitization by siRNA targeting Akt was studied in HEK293 cells forced to express CA-Akt or kinase-dead DN-Akt. To decrease drug resistance, Akt was silenced with siRNA in human prostate DU-145 cell line expressing the normal PTEN or in LNCaP and PC3 cell lines expressing mutated-PTEN. Taxol was used for the chemosensitization studies. RESULTS. Silencing Akt in the drug-resistant CA-Akt cells efficiently sensitized cells to antitubule agents, whereas silencing drug-responsive DN-Akt cells did not. Only minor effects were obtained in wild-type HEK293 cells. Potentiation by siRNA of taxol cytotoxicity was significantly greater in mutated-PTEN cells than in prostate cells expressing wild-type PTEN. The apoptotic program induced by taxol was preferentially potentiated by Akt siRNA in PTEN-mutated cell lines as regards the DU-145 cell line. CONCLUSIONS. Silencing Akt in PTEN-mutated prostate cancer cells enhances the antitumor effects of taxol. No siRNA chemosensitization was obtained in prostate cells with wild type PTEN.
| Original language | English |
|---|---|
| Pages (from-to) | 782-789 |
| Number of pages | 8 |
| Journal | Prostate |
| Volume | 67 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - May 15 2007 |
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Keywords
- Akt
- Chemosensitization
- Prostate cancer
- siRNA
ASJC Scopus subject areas
- Urology
Cite this
Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. / Priulla, Marcella; Calastretti, Angela; Bruno, Paola; Amalia, Azzariti; Paradiso, Angelo; Canti, Gianfranco; Nicolin, Angelo.
In: Prostate, Vol. 67, No. 7, 15.05.2007, p. 782-789.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase
AU - Priulla, Marcella
AU - Calastretti, Angela
AU - Bruno, Paola
AU - Amalia, Azzariti
AU - Paradiso, Angelo
AU - Canti, Gianfranco
AU - Nicolin, Angelo
PY - 2007/5/15
Y1 - 2007/5/15
N2 - BACKGROUND. In prostate cancer, mutations of the phosphatase PTEN can activate the kinase cascade PI3K/Akt/mTOR which induces drug resistance. METHODS. Chemosensitization by siRNA targeting Akt was studied in HEK293 cells forced to express CA-Akt or kinase-dead DN-Akt. To decrease drug resistance, Akt was silenced with siRNA in human prostate DU-145 cell line expressing the normal PTEN or in LNCaP and PC3 cell lines expressing mutated-PTEN. Taxol was used for the chemosensitization studies. RESULTS. Silencing Akt in the drug-resistant CA-Akt cells efficiently sensitized cells to antitubule agents, whereas silencing drug-responsive DN-Akt cells did not. Only minor effects were obtained in wild-type HEK293 cells. Potentiation by siRNA of taxol cytotoxicity was significantly greater in mutated-PTEN cells than in prostate cells expressing wild-type PTEN. The apoptotic program induced by taxol was preferentially potentiated by Akt siRNA in PTEN-mutated cell lines as regards the DU-145 cell line. CONCLUSIONS. Silencing Akt in PTEN-mutated prostate cancer cells enhances the antitumor effects of taxol. No siRNA chemosensitization was obtained in prostate cells with wild type PTEN.
AB - BACKGROUND. In prostate cancer, mutations of the phosphatase PTEN can activate the kinase cascade PI3K/Akt/mTOR which induces drug resistance. METHODS. Chemosensitization by siRNA targeting Akt was studied in HEK293 cells forced to express CA-Akt or kinase-dead DN-Akt. To decrease drug resistance, Akt was silenced with siRNA in human prostate DU-145 cell line expressing the normal PTEN or in LNCaP and PC3 cell lines expressing mutated-PTEN. Taxol was used for the chemosensitization studies. RESULTS. Silencing Akt in the drug-resistant CA-Akt cells efficiently sensitized cells to antitubule agents, whereas silencing drug-responsive DN-Akt cells did not. Only minor effects were obtained in wild-type HEK293 cells. Potentiation by siRNA of taxol cytotoxicity was significantly greater in mutated-PTEN cells than in prostate cells expressing wild-type PTEN. The apoptotic program induced by taxol was preferentially potentiated by Akt siRNA in PTEN-mutated cell lines as regards the DU-145 cell line. CONCLUSIONS. Silencing Akt in PTEN-mutated prostate cancer cells enhances the antitumor effects of taxol. No siRNA chemosensitization was obtained in prostate cells with wild type PTEN.
KW - Akt
KW - Chemosensitization
KW - Prostate cancer
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=34248198039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34248198039&partnerID=8YFLogxK
U2 - 10.1002/pros.20566
DO - 10.1002/pros.20566
M3 - Article
C2 - 17373720
AN - SCOPUS:34248198039
VL - 67
SP - 782
EP - 789
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 7
ER -