Expression and responsiveness of P2Y2 receptors in human endometrial cancer cell lines

J Clin Endocrinol Metab. 1999 Nov;84(11):4085-91. doi: 10.1210/jcem.84.11.6119.


In single endometrial carcinoma HEC-1A and Ishikawa cells, ATP induced a rapid and extracellular Ca2+-independent rise in cytosolic Ca2+ concentration ([Ca2+]i) in a dose-dependent manner, with an ED50 of about 10 microM. The spike phase was followed by a sustained plateau phase that was dependent on Ca2+ influx through voltage-insensitive Ca2+ channels, whose gating was controlled by a capacitative Ca2+ entry mechanism. ADP was less potent in raising the cystolic Ca2+ concentration, and AMP and adenosine were ineffective. The order of agonist potency for this receptor was ATP = UTP > ATP-gamma-S >> ADP. Several other agonists, including beta,gamma-methylene-ATP, 2-MeS-ATP, and BzATP were ineffective. This ligand-selective profile indicates the expression of the P2Y2R subtype in endometrial cells. Accordingly, reverse transcription-PCR using P2Y2 primers amplified the expected transcript from both cell lines. The coupling of these receptors to phospholipase C was confirmed by the ability of ATP to increase inositol 1,4,5-trisphosphate and diacylglycerol productions. These receptors are also coupled to the phospholipase D-1 pathway, leading to accumulation of phosphatidic acid. Activation of P2Y2 receptors by a slowly degradable ATP analog, ATP-gamma-S, was associated with a significant suppression of cell proliferation without affecting the cellular apoptosis. These results indicate that P2Y2 receptors may participate in control of the cell cycle of endometrial carcinoma cells.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / pharmacology
  • Apoptosis
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channels / physiology
  • Cell Division
  • Diglycerides / biosynthesis
  • Endometrial Neoplasms / metabolism*
  • Female
  • Gene Expression* / drug effects
  • Humans
  • Inositol 1,4,5-Trisphosphate / biosynthesis
  • Ion Channel Gating
  • Phosphatidic Acids / metabolism
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2 / physiology*
  • Receptors, Purinergic P2Y2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • Type C Phospholipases / metabolism
  • Uridine Triphosphate / pharmacology


  • Calcium Channels
  • Diglycerides
  • P2RY2 protein, human
  • Phosphatidic Acids
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y2
  • Adenosine Diphosphate
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • Type C Phospholipases
  • Calcium
  • Uridine Triphosphate