title: [Mechanism of the activation of extracellular signal-regulated kinase (ERK) in prostate cancer cell lines with different metastatic potential].
abstract: OBJECTIVE
  To investigate the mechanism of the activation of signal transduction of ERK induced by purinergic receptor agonist ATP in prostate cancer cells with different metastatic potential.
  
  
  METHODS
  Cell counts and MTT method were used to detect the influence of ATP on the growth of 1E8 (metastatic) and 2B4 (non-metastatic) cells derived from human prostate cancer cell line PC3M. The activity of ERK1/2 was analyzed with phosphospecific antibodies directed against the dually phosphorylated, active forms of ERK1/2 (p44/p42) by Western Blot.
  
  
  RESULTS
  ATP can significantly inhibit the growth of 1E8 and 2B4 cells in vitro (inhibition rate in the 6th and the 8th day were 54% and 59% for 1E8 and 67% and 39% for 2B4 respectively). ATP activated both ERK1 and ERK2 in 1E8 and 2B4 cells with a time and dose dependent pattern. The activation of ERK1/2 by ATP was blocked by the P2 purinoceptor antagonist, suramin with an inhibitory rate of 82% +/- 9% for 1E8 and an inhibitory rate of 81% +/- 6% for 2B4. The activation of ERK1/2 by ATP can be inhibited by the inhibitor of the upstream kinase MEK- PD098059 with an inhibitory rate of 94% +/- 4% for 1E8 and 91% +/- 4% for 2B4,which suggests a link between the G protein coupled P2 purinoceptor and activation of Ras MEK MAPK pathway. ATP-stimulated ERK activation was sensitive to treatment with G protein modulator pertussis toxin (PTX) with an inhibitory rate of 50% +/- 3% for 1E8 and 51% +/- 4% for 2B4. The activating potential of ATP to ERK1/2 in metastatic 1E8 cells is greater than that to nonmetastatic 2B4 cells, and the response of 1E8 cells to TPA was quite different from the response of 2B4 cells, thus implying a potential signaling mechanism in regulating metastasis phenotypes.
  
  
  CONCLUSIONS
  The metastatic 1E8 and non-metastatic 2B4 cells show differential response to ATP-induced ERK activation. This may provide an instructive clue to cancer metastasis research.
authors.affiliation: Department of Pathology, Peking University Health Science Center, Beijing 100083, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000266:Adenylyl Imidodiphosphate / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000032:analysis / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D018048:Receptors, Purinergic P2; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D013755:Tetradecanoylphorbol Acetate