HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Role of protein kinase C-iota in transformed non-malignant RWPE-1 cells and androgen-independent prostate carcinoma DU-145 cells.

AbstractUNLABELLED:
Prostate cancer is one of the leading causes of death among men in the USA.
OBJECTIVE:
In this study, we investigated the role of atypical protein kinase C-iota (PKC-iota) in androgen independent prostate DU-145 carcinoma cellscompared to transformed non-malignant prostate RWPE-1 cells.
MATERIALS AND METHODS:
Western blotting and immunoprecipitations demonstrated that PKC-iotaisassociated with cyclin-dependent kinase activating kinase (CAK/Cdk7) in RWPE-1 cells, but not in DU-145 cells.
RESULTS:
Treatment of prostate RWPE-1 cells with PKC-iota silencing RNA (siRNA) decreased cell viability,cell-cycle accumulation at G2/M phase, and phosphorylation of Cdk7 and Cdk2. In addition, PKC-iota siRNA treatment caused less phosphorylation ofBad at ser-155, ser-136, and greater Bad/Bcl-xL heterodimerization, leading to apoptosis. In DU-145 cells, PKC-iota was anti-apoptotic and was required for cell survival. Treatment with PKC-iota siRNA blocked increase in cell number, and inhibited G1/S transition by accumulation of cells in G0/G1phase. In addition to cell-cycle arrest, both RWPE-1 and DU-145 cells underwent apoptosis due to mitochondrial dysfunction and apoptosis cascades, such as release of cytochrome c,activation of caspase-7, and poly (ADP-ribose)polymerase (PARP) cleavage.
CONCLUSION:
Our results suggest that PKC-iota is required for cell survival in both transformed non-malignant prostate RWPE-1 cells and androgen-independent malignant prostate DU-145 cells, whereas suppressing PKC-iota lead to apoptosis in DU-145 prostate cells.
AuthorsH Y Win, M Acevedo-Duncan
JournalCell proliferation (Cell Prolif) Vol. 42 Issue 2 Pg. 182-94 (Apr 2009) ISSN: 1365-2184 [Electronic] England
PMID19243387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • BAD protein, human
  • BCL2L1 protein, human
  • Isoenzymes
  • RNA, Small Interfering
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Poly(ADP-ribose) Polymerases
  • Protein Kinase C
  • protein kinase C lambda
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases
  • Cyclin-Dependent Kinase-Activating Kinase
  • CDK7 protein, human
Topics
  • Apoptosis (physiology)
  • Cell Count
  • Cell Cycle (physiology)
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Survival (physiology)
  • Cyclin-Dependent Kinase 2 (metabolism)
  • Cyclin-Dependent Kinases (metabolism)
  • Humans
  • Isoenzymes (metabolism, physiology)
  • Male
  • Phosphorylation
  • Poly(ADP-ribose) Polymerases (metabolism)
  • Prostate (enzymology, metabolism, pathology)
  • Prostatic Neoplasms (enzymology, metabolism, pathology)
  • Protein Kinase C (metabolism, physiology)
  • RNA, Small Interfering (genetics)
  • bcl-Associated Death Protein (metabolism)
  • bcl-X Protein (metabolism)
  • Cyclin-Dependent Kinase-Activating Kinase

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: