Dual effect of pituitary adenylate cyclase activating polypeptide on prostate tumor LNCaP cells: Short and long-term exposure affect proliferation and neuroendocrine differentiation

Donatella Farini, Antonella Puglianiello, Caterina Mammi, Gregorio Siracusa, Costanzo Moretti

Research output: Contribution to journalArticle

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that elicits the increase of intracellular cAMP levels and protein kinase A activity in various cell systems. Here we show that the pattern of cAMP elevation triggered by PACAP is critical for the fate of LNCaP prostate cancer cells. We demonstrate that these cells express PACAP and its type 1 receptor. A short-term stimulation with PACAP, which generates a transient cAMP rise, induces proliferation of LNCaP cells through a protein kinase A-dependent activation of the MAPK cascade. On the contrary, we observed that chronic PACAP stimulation, giving rise to a sustained cAMP accumulation, leads to proliferation arrest and neuroendocrine differentiation. Moreover, PACAP stimulates phosphorylation and activation of the cAMP response element binding transcription factor (CREB), and MAPK activation is necessary for its full transcriptional activity, indicating a direct involvement of cAMP response element in PACAP action. These findings demonstrate that a crucial event determining the outcome of prostatic cancer cells progression is the sustained vs. transient intracellular cAMP increase.

Original languageEnglish
Pages (from-to)1631-1643
Number of pages13
JournalEndocrinology
Volume144
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

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ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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