| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 3, 2005
Accepted on September 27, 2005
Institute of Endocrine Sciences, Fondazione Ospedale Maggiore IRCCS (G.M, S.B., B.G., S.C., E.F., E.P., P.B-P., A.S., A.G.L.), Pathology Unit, Department of Medicine, Surgery and Dentistry, A.O. San Paolo and Ospedale Maggiore IRCCS (S.F.) and Department of Neurosurgery, Ospedale Maggiore IRCCS (M.L., P.R.); University of Milan, Milan, Italy
* To whom correspondence should be addressed. E-mail: anna.spada{at}unimi.it.
Context Alterations in cAMP signaling have been identified as cause of endocrine neoplasia. In particular, activating mutations of the Gs
gene and protein kinase A (PKA) overactivity due to low expression of protein kinase A (PKA) regulatory subunit 1A (R1A) have been implicated in somatotroph proliferation.
Objective To evaluate the effects of cAMP-PKA cascade activation in non-functioning pituitary adenomas (NFPA).
Design and Methods By immunohistochemistry (IHC) R1A, R2A and R2B expression was evaluated in cells obtained form 8 surgically removed NFPA positive for gonadotropins. Cyclin D1 expression and extracellular signal-regulated kinase (ERK1/2) activity were analyzed in basal conditions and after cAMP-PKA cascade activation.
Results IHC studies demonstrated a low R1/R2 ratio in all NFPA. Further unbalance of R1/R2 ratio by 8-Cl-cAMP and direct adenylyl cyclase stimulation by forskolin did not increase cyclin D1 expression or ERK1/2 activity in 5 NFPA (Group 1), but even caused a 74 ± 15% and 85 ± 13% inhibition of cyclin D1 and ERK1/2 activity, respectively, in the remaining (Group 2). Moreover, in Group 2, PKA blockade by the specific inhibitor PKI increased cyclin D1 expression (96 ± 25% over basal) and ERK1/2 activity (116 ± 28% over basal).
Conclusions These data show that, in contrast with what previously observed in transformed somatotrophs, the activation of cAMP-PKA pathway did not generate proliferative signals in tumoral cells of the gonadotroph lineage and in a subset of tumors even exerted a tonic inhibitory effect, thus confirming a different role of cAMP-mediated pathway in promoting proliferation in the pituitary.
This article has been cited by other articles:
 |
|
 |
|
  T. Florio, F. Barbieri, R. Spaziante, G. Zona, L. J Hofland, P. M van Koetsveld, R. A Feelders, G. K Stalla, M. Theodoropoulou, M. D Culler, et al. Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center study Endocr. Relat. Cancer, June 1, 2008; 15(2): 583 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yin, L. Williams-Simons, A. F. Parlow, S. Asa, and L. S. Kirschner Pituitary-Specific Knockout of the Carney Complex Gene Prkar1a Leads to Pituitary Tumorigenesis Mol. Endocrinol., February 1, 2008; 22(2): 380 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Al-Dhaheri and B. G. Rowan Protein Kinase A Exhibits Selective Modulation of Estradiol-Dependent Transcription in Breast Cancer Cells that Is Associated with Decreased Ligand Binding, Altered Estrogen Receptor {alpha} Promoter Interaction, and Changes in Receptor Phosphorylation Mol. Endocrinol., February 1, 2007; 21(2): 439 - 456. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
