scholarly journals Differential roles and activation of mammalian target of rapamycin complexes 1 and 2 during cell migration in prostate cancer cells

The Prostate ◽  
2020 ◽  
Vol 80 (5) ◽  
pp. 412-423 ◽  
Author(s):  
Smrruthi Vaidegi Venugopal ◽  
Silvia Caggia ◽  
DaJhnae Gambrell‐Sanders ◽  
Shafiq A. Khan
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Prostate Cancer Cells

scholarly journals TGF-β Effects on Prostate Cancer Cell Migration and Invasion Are Mediated by PGE2 through Activation of PI3K/AKT/mTOR Pathway

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1768-1779 ◽  
Author(s):  
BaoHan T. Vo ◽  
Derrick Morton ◽  
Shravan Komaragiri ◽  
Ana C. Millena ◽  
Chelesie Leath ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Protein Levels ◽  
Prostate Cells ◽  
Pc3 Cells ◽  
Cox 2

Abstract TGF-β plays an important role in the progression of prostate cancer. It exhibits both tumor suppressor and tumor-promoting activities. Correlations between cyclooxygenase (COX)-2 overexpression and enhanced production of prostaglandin (PG)E2 have been implicated in cancer progression; however, there are no studies indicating that TGF-β effects in prostate cancer cells involve PGE2 synthesis. In this study, we investigated TGF-β regulation of COX-1 and COX-2 expression in prostate cancer cells and whether the effects of TGF-β on cell proliferation and migration are mediated by PGE2. COX-1 protein was ubiquitously expressed in prostate cells; however, COX-2 protein levels were detected only in prostate cancer cells. TGF-β treatment increased COX-2 protein levels and PGE2 secretion in PC3 cells. Exogenous PGE2 and PGF2α had no effects on cell proliferation in LNCaP, DU145, and PC3 cells whereas PGE2 and TGF-β induced migration and invasive behavior in PC3 cells. Only EP2 and EP4 receptors were detected at mRNA levels in prostate cells. The EP4-targeting small interfering RNA inhibited PGE2 and TGF-β-induced migration of PC3 cells. TGF-β and PGE2 induce activation of PI3K/AKT/mammalian target of rapamycin pathway as indicated by increased AKT, p70S6K, and S6 phosphorylation. Rapamycin completely blocked the effects of TGF-β and PGE2 on phosphorylation of p70S6K and S6 but not on AKT phosphorylation. PGE2 and TGF-β induced phosphorylation of AKT, which was blocked by antagonists of PGE2 (EP4) receptors (L161982, AH23848) and PI3K inhibitor (LY294002) in PC3 cells. Pretreatment with L161982 or AH23848 blocked the stimulatory effects of PGE2 and TGF-β on cell migration, whereas LY294002 or rapamycin completely eliminated PGE2, TGF-β, and epidermal growth factor-induced migration in PC3 cells. We conclude that TGF-β increases COX-2 levels and PGE2 secretion in prostate cancer cells which, in turn, mediate TGF-β effects on cell migration and invasion through the activation of PI3K/AKT/mammalian target of rapamycin pathway.

scholarly journals Inhibition of Mammalian Target of Rapamycin or Apoptotic Pathway Induces Autophagy and Radiosensitizes PTEN Null Prostate Cancer Cells

2006 ◽  
Vol 66 (20) ◽  
pp. 10040-10047 ◽  
Author(s):  
Carolyn Cao ◽  
Ty Subhawong ◽  
Jeffrey M. Albert ◽  
Kwang Woon Kim ◽  
Ling Geng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Prostate Cancer Cells ◽  
Apoptotic Pathway

A Novel Semisynthetic Inhibitor of the FRB Domain of Mammalian Target of Rapamycin Blocks Proliferation and Triggers Apoptosis in Chemoresistant Prostate Cancer Cells

2012 ◽  
Vol 83 (2) ◽  
pp. 531-541 ◽  
Author(s):  
Samy A. F. Morad ◽  
Maximilian Schmid ◽  
Berthold Büchele ◽  
Hans-Ullrich Siehl ◽  
Menna El Gafaary ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Prostate Cancer Cells
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