Growth-regulatory effect of gastrin on human colon cancer cell lines is determined by protein kinase a isoform content

Regul Pept. 1994 Aug 31;53(1):61-70. doi: 10.1016/0167-0115(94)90159-7.


Cell growth is regulated by various peptide growth factors through receptor-linked multiple intracellular signal-transduction pathways, such as the cyclic adenosine monophosphate (cAMP) pathway. cAMP activates cAMP-dependent protein kinase A (PKA) either to stimulate or inhibit cell growth. The effect on growth is determined by the presence of two isoforms of the regulatory (R) subunit of PKA; activation of RI alpha-type PKA leads to stimulation of growth, activation of RII beta-type inhibits cell growth. We determined whether the effect of gastrin on the growth of human colon cancer cells is determined by cell-specific content of PKA. We utilized two human colon cancer cell lines: LoVo, growth of which is stimulated by gastrin, and HCT116, growth of which is inhibited by gastrin. Activation of both types of PKA with 8-Br-cAMP mimicked the regulation of growth by gastrin; preferential activation of RII beta-type PKA with 8-Cl-cAMP inhibited growth of both cell lines. LoVo cells possess the predominantly RI alpha isoform of PKA at the mRNA and protein level; HCT116 cells possess predominantly the RII beta-type PKA. The cAMP-mediated regulation of growth (either stimulatory or inhibitory) by gastrin on these human colon cancer cells was determined by the predominant isoform of PKA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Cell Division / drug effects
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology*
  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Gastrins / pharmacology*
  • Humans
  • Isoenzymes / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured


  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Gastrins
  • Isoenzymes
  • PRKAR1A protein, human
  • PRKAR2B protein, human
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Cyclic AMP-Dependent Protein Kinases