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Effects of extracellular nucleotides and nucleosides on prostate carcinoma cells

R Janssens1, J M Boeynaems

  • 1Institute of Interdisciplinary Research, School of Medicine, Université Libre de Bruxelles, 1070 Brussels, Belgium. r_janssens@hotmail.com

British Journal of Pharmacology
|February 13, 2001
PubMed

Insights

This study investigated nucleotide receptors in human prostate cancer cells. P2Y and P2X receptors were identified, influencing cell growth and function, suggesting P2X receptors may inhibit prostate carcinoma cell proliferation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Nucleotide signaling plays a role in various cellular processes.
  • Understanding receptor involvement in cancer is crucial for therapeutic development.
  • Prostate carcinoma cell lines LNCaP, PC-3, and DU145 are models for studying prostate cancer.

Purpose of the Study:

  • To characterize nucleotide receptors in human prostate carcinoma cell lines.
  • To investigate the functional roles of these receptors in cell signaling and growth.
  • To explore the potential involvement of purinergic receptors in inhibiting prostate cancer cell proliferation.

Main Methods:

  • Northern blotting to detect messenger RNA (mRNA) expression of P2Y receptors.
  • RT-PCR to detect P2X receptor expression.
  • Measurement of inositol phosphate accumulation and cyclic AMP levels.
  • Assessment of calcium influx.
  • Cell growth inhibition assays and apoptosis/necrosis analysis.

Main Results:

  • P2Y(2), P2Y(6), and P2Y(11) mRNA were detected in all three cell lines; P2Y(1) mRNA was specific to DU145 cells.
  • ATP and UTP stimulated inositol phosphate accumulation, implicating P2Y(2) receptors.
  • ATP increased cyclic AMP via adenosine and A(2) receptor activation, enhancing prostate-specific antigen secretion.
  • P2X(4), P2X(5), and P2X(7) receptors were expressed in PC-3 and DU145 cells, confirmed by calcium influx.
  • ATP inhibited PC-3 and DU145 cell growth; BzATP mimicked this effect in PC-3 cells, increasing apoptosis.
  • In DU145 cells, ATP was more potent than BzATP, with growth inhibition primarily via necrosis.

Conclusions:

  • Human prostate carcinoma cell lines express various P2Y and P2X purinergic receptors.
  • P2Y(2) receptors mediate inositol phosphate accumulation, while P2X receptors are involved in ATP-induced growth inhibition.
  • P2X receptors may play a significant role in inhibiting prostate carcinoma cell growth, suggesting potential therapeutic targets.

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