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Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells
08:31

Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells

Published on: February 18, 2016

Effect of cyclic adenosine 3',5'-monophosphate/protein kinase a pathway on markers of cell proliferation in

G Mantovani1, S Bondioni, S Ferrero

  • 1Institute of Endocrine Sciences, Ospedale Maggiore, IRCCS, University of Milan, Italy.

The Journal of Clinical Endocrinology and Metabolism
|October 6, 2005
PubMed
Abstract

Insights

Activating the cAMP-PKA pathway in nonfunctioning pituitary adenomas (NFPA) did not promote cell proliferation. In some NFPA, this pathway even inhibited tumor cell growth, unlike its effect in somatotroph tumors.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Alterations in cyclic adenosine monophosphate (cAMP) signaling are linked to endocrine neoplasia.
  • Activating G(s)alpha gene mutations and protein kinase A (PKA) overactivity due to low PKA regulatory subunit 1A (R1A) expression are implicated in somatotroph proliferation.

Purpose of the Study:

  • To investigate the impact of cAMP-PKA cascade activation on nonfunctioning pituitary adenomas (NFPA).

Main Methods:

  • Immunohistochemistry assessed R1A, R2A, and R2B expression in gonadotropin-positive NFPA.
  • Cyclin D1 expression and ERK1/2 activity were measured under basal conditions and after cAMP-PKA activation.

Main Results:

  • NFPA exhibited a low R1/R2 subunit ratio.
  • cAMP-PKA activation inhibited cyclin D1 expression and ERK1/2 activity in a subset of NFPA (group 2).
  • In group 2, PKA inhibition increased cyclin D1 expression and ERK1/2 activity.

Conclusions:

  • cAMP-PKA pathway activation does not induce proliferation in gonadotroph lineage tumoral cells.
  • In a subset of NFPA, the cAMP-PKA pathway exerts a tonic inhibitory effect on proliferation.
  • The role of cAMP-mediated pathways in pituitary tumor proliferation differs between cell lineages.

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