Document Detail


Bone morphogenetic protein-4 inhibits corticotroph tumor cells: involvement in the retinoic acid inhibitory action.
MedLine Citation:
PMID:  16195406     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.
Authors:
Damiana Giacomini; Marcelo Páez-Pereda; Marily Theodoropoulou; Marta Labeur; Damian Refojo; Juan Gerez; Alberto Chervin; Silvia Berner; Marco Losa; Michael Buchfelder; Ulrich Renner; Günter K Stalla; Eduardo Arzt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-09-29
Journal Detail:
Title:  Endocrinology     Volume:  147     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-20     Completed Date:  2006-02-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  247-56     Citation Subset:  AIM; IM    
Affiliation:
Laboratorio de Fisiología y Biología Molecular, Departemento de Fisiología, Biología Molecular y Celular, Facultad Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, 1428 Buenos Aires, Argentina.
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MeSH Terms
Descriptor/Qualifier:
Adenoma / pathology*
Animals
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins / pharmacology*,  physiology*
Cell Division / drug effects
Cell Line, Tumor
Cushing Syndrome / pathology*
Humans
Immunohistochemistry
Mice
Pituitary Gland / pathology,  physiology
Pituitary Neoplasms / pathology*
Reference Values
Tretinoin / pharmacology*
Chemical
Reg. No./Substance:
0/BMP4 protein, human; 0/Bmp4 protein, mouse; 0/Bone Morphogenetic Protein 4; 0/Bone Morphogenetic Proteins; 302-79-4/Tretinoin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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