Elevation of cyclic adenosine 3',5'-monophosphate potentiates activation of mitogen-activated protein kinase by growth factors in LNCaP prostate cancer cells

Taosheng Chen, Richard W. Cho, Philip Stork, Michael J. Weber

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Prostate cells are simultaneously exposed to a variety of peptide growth factors and neuropeptides that elevate cAMP. Both the growth factors and cAMP have large effects on the growth, differentiation, and movement of many cell types. Because mitogen-activated protein kinase (MAPK) is central to these effects, we analyzed the ways in which these agonists interact in regulating MAPK in prostate cancer cells. We show that, in LNCaP prostate cancer cells, elevation of intracellular cAMP can potentiate the ability of epidermal growth factor (EGF), interleukin 6, and serum to activate MAPK and that this potentiation depends on protein kinase A and Rap1. The response to cAMP is different in the androgen-independent prostate cancer cell line PC-3, where elevation of cAMP slightly inhibits MAPK activation by EGF. We also show that treatment of LNCaP with the calcium ionophore A23187 or the phorbol ester phorbol 12-myristate 13-acetate activates MAPK, but the activation of MAPK by these agonists is inhibited rather than potentiated by increasing cAMP. Finally, we show that phorbol 12-myristate 13-acetate and interleukin 6 can potentiate the signaling activity of EGF. We conclude that neuroendocrine factors that elevate cAMP sensitize LNCaP prostate cancer cells to signaling by peptide growth factors and that low levels of mixtures of growth factors can activate intracellular signaling to a greater degree than would be predicted from the activity of the individual agonists.

Original languageEnglish (US)
Pages (from-to)213-218
Number of pages6
JournalCancer Research
Volume59
Issue number1
StatePublished - Jan 1 1999

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Mitogen-Activated Protein Kinases
Cyclic AMP
Prostatic Neoplasms
Intercellular Signaling Peptides and Proteins
Epidermal Growth Factor
Interleukin-6
Acetates
Peptides
Calcium Ionophores
Calcimycin
Phorbol Esters
Cyclic AMP-Dependent Protein Kinases
Neuropeptides
Androgens
Cell Movement
Prostate
Cell Line
Growth
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Elevation of cyclic adenosine 3',5'-monophosphate potentiates activation of mitogen-activated protein kinase by growth factors in LNCaP prostate cancer cells. / Chen, Taosheng; Cho, Richard W.; Stork, Philip; Weber, Michael J.

In: Cancer Research, Vol. 59, No. 1, 01.01.1999, p. 213-218.

Research output: Contribution to journalArticle

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