Mammalian target of rapamycin and 3-phosphatidylinositol 3-kinase pathway inhibition enhances growth inhibition of transforming growth factor-beta1 in prostate cancer cells

The Journal of Urology
H G van der Poel

Abstract

Serum transforming growth factor (TGF)-beta1 is elevated in patients with metatatic prostate cancer. Although growth inhibitory in normal prostate epithelial cells, cancer cells are often resistant to TGF-beta1. The role of phosphatidylinositol 3-kinase (PI3K)/AKT and mammalian target of rapamycin (mTOR) signaling in TGF-beta1 resistance was studied in prostate cancer cell lines. PC3 and LNCaP human prostate cancer cell lines were exposed for 72 hours to rapamycin (mTOR inhibition), LY294002 (PI3K/AKT inhibition) and TGF-beta1 in a proliferation (WST-1) assay. A TGF-beta1 receptor II, stably transfected LNCaP cell line was used (LNCaP-RII). TGF-beta1/SMAD (Sma and MAD [mothers-against-decapentaplegic]homologue) signaling was assessed using the pGL3-SBE4-luc (SBE4) reporter plasmid. Immunoblotting and immunocytochemistry were applied to evaluate phosphorylated Smad and E-cadherin expression in relation to mTOR inhibition and TGF-beta1 exposure. In PC3 and LNCaP-RII cells mTOR and PI3K/AKT inhibition caused TGF-beta1 to become inhibitory for growth. The synergistic effect was associated with the increased expression of phosphorylated Smad and induction of SBE4 reporter plasmid expression. E-cadherin in PC3 cells increased upon mT...Continue Reading

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Citations

Jul 27, 2011·Human Reproduction Update·Pasquapina CiarmelaMario Castellucci
Jun 11, 2011·Journal of Biomedicine & Biotechnology·Valeria RizzelloGuido Ferlazzo
Feb 9, 2012·Advances in Virology·Christopher A Alvarez-BreckenridgeE Antonio Chiocca
Aug 15, 2009·Journal of the American Society of Nephrology : JASN·Sandhya XavierErwin P Böttinger
Jun 16, 2009·Urologic Oncology·Jaskarn S RaiHari L Ratan
Sep 2, 2006·Critical Reviews in Oncology/hematology·H G van der Poel
May 3, 2006·The Prostate·Celeste L KremerRaymond B Nagle
Dec 6, 2014·Praxis der Kinderpsychologie und Kinderpsychiatrie·Agnes Wyl
Dec 23, 2008·The Biochemical Journal·Stephen J AssinderDes R Richardson
Mar 17, 2005·The International Journal of Artificial Organs·A AguileraR Selgas
Aug 12, 2009·Cellular Signalling·Bashier OsmanWolfgang Eberhardt

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