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

Richard J Bold, Scott Alpard, Jin Ishizuka, Courtney M. Townsend

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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 R-type PKA leads to stimulation of growth, activation of RIIβ-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 RIIβ-type PKA with 8-Cl-cAMP inhibited growth of both cell lines. LoVo cells possess the predominantly R isoform of PKA at the mRNA and protein level; HCT116 cells possess predominantly the RIIβ-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.

Original languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalRegulatory Peptides
Volume53
Issue number1
DOIs
StatePublished - Aug 31 1994
Externally publishedYes

Keywords

  • Colon cancer
  • Cyclic AMP
  • Regulatory subunit

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Growth-regulatory effect of gastrin on human colon cancer cell lines is determined by protein kinase a isoform content'. Together they form a unique fingerprint.

  • Cite this