Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase

Marcella Priulla, Angela Calastretti, Paola Bruno, Azzariti Amalia, Angelo Paradiso, Gianfranco Canti, Angelo Nicolin

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish
Pages (from-to)782-789
Number of pages8
JournalProstate
Volume67
Issue number7
DOIs
Publication statusPublished - May 15 2007

Fingerprint

Prostate
Phosphotransferases
Small Interfering RNA
Paclitaxel
Cell Line
HEK293 Cells
Drug Resistance
Prostatic Neoplasms
PTEN Phosphohydrolase
Phosphatidylinositol 3-Kinases
Pharmaceutical Preparations
Mutation

Keywords

  • Akt
  • Chemosensitization
  • Prostate cancer
  • siRNA

ASJC Scopus subject areas

  • Urology

Cite this

Priulla, M., Calastretti, A., Bruno, P., Amalia, A., Paradiso, A., Canti, G., & Nicolin, A. (2007). Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. Prostate, 67(7), 782-789. https://doi.org/10.1002/pros.20566

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 journalArticle

Priulla, M, Calastretti, A, Bruno, P, Amalia, A, Paradiso, A, Canti, G & Nicolin, A 2007, 'Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase', Prostate, vol. 67, no. 7, pp. 782-789. https://doi.org/10.1002/pros.20566
Priulla, Marcella ; Calastretti, Angela ; Bruno, Paola ; Amalia, Azzariti ; Paradiso, Angelo ; Canti, Gianfranco ; Nicolin, Angelo. / Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. In: Prostate. 2007 ; Vol. 67, No. 7. pp. 782-789.
@article{b67977fd85d24ab0b3f7ca93736e472a,
title = "Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase",
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.",
keywords = "Akt, Chemosensitization, Prostate cancer, siRNA",
author = "Marcella Priulla and Angela Calastretti and Paola Bruno and Azzariti Amalia and Angelo Paradiso and Gianfranco Canti and Angelo Nicolin",
year = "2007",
month = "5",
day = "15",
doi = "10.1002/pros.20566",
language = "English",
volume = "67",
pages = "782--789",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "7",

}

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 -