Prolactin stimulation of ornithine decarboxylase and mitogenesis in Nb2 node lymphoma cells: The role of protein kinase C and calcium mobilization

Arthur R. Buckley, David W. Montgomery, Ruthann Kibler, Charles W. Putnam, Charles F. Zukoski, Peter W. Gout, Charles T. Beer, Diane Haddock Russell

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with calcium ionophores has been shown to bypass the requisite antigen- or lectin-induced signal for lymphocyte mitogenesis. This suggests that protein kinase C activation and calcium mobilization may be early events required for lymphocyte proliferation. Therefore, the relationship(s) of protein kinase C activation and calcium mobilization to ornithine decarboxylase induction and cellular proliferation were examined in a rat node lymphoma cell line (Nb2) which is dependent upon prolactin (PRL) for mitogenesis. TPA enhanced PRL-stimulated Nb2 node lymphoma cell ornithine decarboxylase induction and [3H]thymidine incorporation. Addition of a calcium ionophore (A23187) to cultures containing TPA plus PRL increased ornithine decarboxylase above PRL alone or PRL plus TPA but inhibited proliferation compared to the PRL plus TPA regimen. Exposure of cells to TPA or TPA plus A23187 increased [3H]thymidine incorporation in a similar manner to that demonstrated for low-dose PRL. However, optimal concentrations were only 20-25% as effective as mitogens as was optimal PRL. Protein kinase C and calmodulin antagonists inhibited PRL-stimulated ornithine decarboxylase induction and proliferation. Ca2+ chelation or cation channel antagonism inhibited both PRL-stimulated responses. The cyclic AMP analogue, 8Br-cAMP, inhibited PRL-stimulated ornithine decarboxylase activity as well as cellular proliferation process assessed by [3H]thymidine incroporation. Finally, tumor-promoting phorbol esters inhibited 125I-rPRL binding. These data strongly suggest that protein kinase C activation and calcium mobilization are requisite events for PRL-stimulated ornithine decarboxylase induction and cellular proliferation in Nb2 node lymphoma cells. An additional component that is linked to alterations in K+ channeling is also implicated. These data support a role for protein kinase C in PRL-coupled mitogenesis. However, other critical Ca2+ and/or ion-induced events are also required.

Original languageEnglish (US)
Pages (from-to)37-51
Number of pages15
JournalImmunopharmacology
Volume12
Issue number1
DOIs
StatePublished - Aug 1986
Externally publishedYes

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Keywords

  • Calcium ionophore
  • Calmodulin
  • Cellular proliferation
  • Ornithine decarboxylase
  • Phorbol ester
  • Prolactin
  • Protein kinase C
  • Receptor coupling

ASJC Scopus subject areas

  • Pharmacology

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