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 Citations (Scopus)

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

Fingerprint

Gastrins
Cyclic AMP-Dependent Protein Kinases
Colonic Neoplasms
Protein Kinases
Protein Isoforms
Cells
Cell Line
Cyclic AMP
Growth
Cell growth
Chemical activation
Signal transduction
HCT116 Cells
Growth Factor Receptors
Intercellular Signaling Peptides and Proteins
Signal Transduction
Messenger RNA
Peptides

Keywords

  • Colon cancer
  • Cyclic AMP
  • Regulatory subunit

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Growth-regulatory effect of gastrin on human colon cancer cell lines is determined by protein kinase a isoform content. / Bold, Richard J; Alpard, Scott; Ishizuka, Jin; Townsend, Courtney M.

In: Regulatory Peptides, Vol. 53, No. 1, 31.08.1994, p. 61-70.

Research output: Contribution to journalArticle

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