PTPL1 and PKCδ contribute to proapoptotic signalling in prostate cancer cells

Cell Death Dis. 2013 Apr 4;4(4):e576. doi: 10.1038/cddis.2013.90.

Abstract

PTPL1 is a non-receptor protein tyrosine phosphatase involved in apoptosis regulation, although controversial findings have been reported in different cancer types. We report here a proapoptotic role for PTPL1 in PC3 and LNCaP prostate cancer cells, as its absence induces apoptosis resistance upon treatment with different drugs. In PC3 cells, PTPL1 silencing by small interfering RNA influences the expression levels of Bcl-xL and Mcl-1(S) proteins as well as final events in the apoptotic process such as activation of caspases and caspase-mediated cleavage of proteins like Mcl-1 or poly (ADP-ribose) polymerase. We have identified PKCδ as an intermediary of PTPL1-mediated apoptotic signalling and that phosphorylation status of NF-κB and IκBα is influenced by PTPL1 and PKCδ. Furthermore, the loss of PTPL1 and PKCδ expression in poorly differentiated, more aggressive human prostate cancers also indicate that their absence could be related to apoptosis resistance and tumour progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Male
  • Myeloid Cell Leukemia Sequence 1 Protein
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Protein Kinase C-delta / antagonists & inhibitors
  • Protein Kinase C-delta / genetics*
  • Protein Kinase C-delta / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13 / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering
  • Signal Transduction / genetics*
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • BCL2L1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • bcl-X Protein
  • I-kappa B Kinase
  • Protein Kinase C-delta
  • PTPN13 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13