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[Effects of P2Y receptor activation on prostatic cancer cells requiring ERK1/2 or p38 cascade]

Ling Chen1, Wei-gang Fang, Wan-jie Heng

  • 1Department of Pathology, Peking University Health Science Center, Beijing 100083, China.

Zhonghua Bing Li Xue Za Zhi = Chinese Journal of Pathology
|May 11, 2004
PubMed
Abstract

Insights

Extracellular signal-regulated kinase (ERK1/2) and p38 pathways mediate P2Y receptor effects on prostate cancer cells. Continuous P2Y receptor activation inhibits growth, while transient activation promotes invasion, with ERK1/2 regulating colony formation.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • Prostatic cancer cell behavior is influenced by extracellular signals.
  • P2Y receptors and associated kinase pathways (ERK1/2, p38) are implicated in cancer progression.

Purpose of the Study:

  • To elucidate the roles of extracellular signal-regulated kinase (ERK1/2) and p38 signaling pathways in P2Y receptor-mediated effects on prostatic cancer cells.
  • To investigate how different P2Y receptor activation patterns influence cancer cell growth, colony formation, and invasion.

Main Methods:

  • Prostatic cancer cells (1E8) were transfected with dominant-negative MAPK kinase 1 (KA-MEK1) to inhibit ERK1/2 activation.
  • Western blot was used to confirm ERK1/2 activation.
  • In vitro growth, soft agar colony formation, and invasion assays were performed.
  • Flow cytometry assessed ATP's effect on apoptosis.
  • Specific inhibitors (SB203580 for p38) were used to dissect pathway involvement.

Main Results:

  • Dominant-negative MEK1 transfection significantly suppressed ERK1/2 activity and inhibited prostatic cancer cell growth by 71%.
  • Continuous ATP treatment further inhibited growth in KA-MEK1 cells, an effect modulated by p38 inhibition, indicating combined ERK1/2 and p38 roles in growth inhibition.
  • ERK1/2, not p38, was crucial for P2Y receptor-mediated inhibition of colony formation.
  • ATP-induced invasion was dependent on both ERK1/2 and p38 pathways, with p38 inhibition blocking ATP's effect on restoring invasion.

Conclusions:

  • P2Y receptor activation by ATP differentially affects prostatic cancer cell behavior based on activation duration.
  • Continuous P2Y receptor activation leads to growth inhibition, while transient activation stimulates invasion.
  • Both ERK1/2 and p38 pathways are critical for ATP-induced growth inhibition and invasion, whereas ERK1/2 alone regulates colony formation.

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