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

doi:10.1016/0167-0115(94)90159-7

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 journal › Article › peer-review

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_Iα-type PKA leads to stimulation of growth, activation of R_IIβ-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 R_IIβ-type PKA with 8-Cl-cAMP inhibited growth of both cell lines. LoVo cells possess the predominantly R_Iα isoform of PKA at the mRNA and protein level; HCT116 cells possess predominantly the R_IIβ-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 language	English (US)
Pages (from-to)	61-70
Number of pages	10
Journal	Regulatory Peptides
Volume	53
Issue number	1
DOIs	https://doi.org/10.1016/0167-0115(94)90159-7
State	Published - Aug 31 1994
Externally published	Yes

Keywords

Colon cancer
Cyclic AMP
Regulatory subunit

ASJC Scopus subject areas

Physiology
Biochemistry
Endocrinology
Clinical Biochemistry
Cellular and Molecular Neuroscience

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10.1016/0167-0115(94)90159-7

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

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 RIα-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 RIα 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.",

keywords = "Colon cancer, Cyclic AMP, Regulatory subunit",

author = "Bold, {Richard J.} and Scott Alpard and Jin Ishizuka and Townsend, {Courtney M.}",

note = "Funding Information: We wish to thank Jell Hsieh and Chu-chi Wang for their technical assistance and Gene Dockal, Daryl Janes, Steve Schuenke, Karen Martin, and Bob Todd for their assistance in the preparation of this manuscript. This study was supported by grants from the American Cancer Society (CB-571), the National Institutes of Health (5R37 DK 15241, PO1 DK 35608) and the Walls Medical Foundation.",

year = "1994",

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doi = "10.1016/0167-0115(94)90159-7",

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T1 - Growth-regulatory effect of gastrin on human colon cancer cell lines is determined by protein kinase a isoform content

AU - Bold, Richard J.

AU - Alpard, Scott

AU - Ishizuka, Jin

AU - Townsend, Courtney M.

N1 - Funding Information: We wish to thank Jell Hsieh and Chu-chi Wang for their technical assistance and Gene Dockal, Daryl Janes, Steve Schuenke, Karen Martin, and Bob Todd for their assistance in the preparation of this manuscript. This study was supported by grants from the American Cancer Society (CB-571), the National Institutes of Health (5R37 DK 15241, PO1 DK 35608) and the Walls Medical Foundation.

PY - 1994/8/31

Y1 - 1994/8/31

N2 - 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 RIα-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 RIα 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.

AB - 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 RIα-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 RIα 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.

KW - Colon cancer

KW - Cyclic AMP

KW - Regulatory subunit

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

Abstract

Keywords

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