Regulation of heat-shock protein (hsp70) gene expression by hGH and IL2 in rat Nb2 lymphoma cells

Mol Cell Endocrinol. 1994 Nov;105(2):139-46. doi: 10.1016/0303-7207(94)90163-5.

Abstract

A comparative study of hGH and IL2 post-signaling effects, as examined by RNA expression (Nb29) and protein levels of the heat-shock protein hsp70, was performed in a hormone-dependent rat lymphoma cell line, Nb2-11C. Optimal doses of hGH or IL2 increased Nb29 expression in a dose-dependent manner. Addition of both mitogens to cell cultures affected Nb29 expression and mitogenesis synergystically, indicating a possible interaction between the post-receptoral mechanisms of these mitogens. Pretreatment of the cells with cholera toxin (CT) inhibited Nb29 expression, protein levels and mitogenesis of hGH- or IL2-induced cells up to 50%, indicating the involvement of Gs-proteins in the post-signaling processes of both hGH and IL2. Incubation of cell cultures with low concentrations of pertussis toxin (IAP) (0.01 ng/ml) markedly increased Nb29 expression in hGH but not in IL2-induced cells, suggesting specific involvement of the Gi-protein in post-signaling processes of hGH-induced cells. Addition of the PKC activator 12-O-tetra-decanoyl phorbol ester (TPA) to control cell cultures markedly increased the expression of Nb29 RNA levels but not mitogenesis, indicating that induction of these proteins in the cells is not sufficient for cell proliferation. Furthermore, incubation of hGH- or IL2-induced cells with the potent PKC inhibitor staurosporin (ST) decreased the levels of Nb29 in both hGH- and IL2-induced cells, although the effect of the mitogens differed significantly in their inhibition slopes. These results indicate that activation of PKC is one of the signaling pathways differentially involved in hGH and IL2 stimulation of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Blotting, Northern
  • Cell Division / drug effects
  • Cholera Toxin / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / physiology
  • GTP-Binding Proteins / physiology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Growth Hormone / pharmacology*
  • HSP70 Heat-Shock Proteins / analysis
  • HSP70 Heat-Shock Proteins / biosynthesis
  • HSP70 Heat-Shock Proteins / genetics*
  • Interleukin-2 / pharmacology*
  • Lymphoma / genetics
  • Lymphoma / metabolism
  • Lymphoma / pathology*
  • Pertussis Toxin
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology
  • Rats
  • Staurosporine
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Alkaloids
  • HSP70 Heat-Shock Proteins
  • Interleukin-2
  • Virulence Factors, Bordetella
  • Growth Hormone
  • Cholera Toxin
  • Pertussis Toxin
  • Protein Kinase C
  • GTP-Binding Proteins
  • Staurosporine
  • Tetradecanoylphorbol Acetate