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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2009-7-16
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pubmed:abstractText |
Bone morphogenetic proteins (BMP) have been shown to affect tumorigenesis in a variety of tumors. Quantitative PCR analysis revealed down-regulation of BMP2 and BMP5 in tissue samples from adrenocortical carcinoma and adrenocortical tumor cell lines compared with normal adrenal glands. Integrity of BMP-dependent pathways in these cell lines could be shown by activation of the Smad1/5/8 pathway with subsequent increase of ID protein expression upon incubation with BMP2 or BMP5. On a functional level, BMP treatment resulted in inhibition of cell proliferation and viability in a dose- and time-dependent manner. This growth inhibitory effect was associated with BMP-dependent reduction of AKT phosphorylation under baseline conditions and under insulin-like growth factor costimulation. Furthermore, steroidogenic function, including melanocortin-2 receptor and steroidogenic enzyme expressions, was profoundly reduced. In vitro demethylation treatment and overexpression of GATA6 resulted in reactivation of BMP-dependent pathways with concomitant modulation of steroidogenesis. Taken together, we show that loss of expression of members of the BMP family of ligands is a common finding in adrenocortical tumors and we provide evidence that BMP-dependent pathways are likely to be involved in the modulation of the malignant and functional phenotype of adrenocortical cancer cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aldosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 5,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/GATA6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrocortisone,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid 17-alpha-Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1538-7445
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
69
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5784-92
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19584291-Adrenal Cortex Neoplasms,
pubmed-meshheading:19584291-Adrenocortical Carcinoma,
pubmed-meshheading:19584291-Aldosterone,
pubmed-meshheading:19584291-Blotting, Western,
pubmed-meshheading:19584291-Bone Morphogenetic Protein 2,
pubmed-meshheading:19584291-Bone Morphogenetic Protein 5,
pubmed-meshheading:19584291-Bone Morphogenetic Protein Receptors,
pubmed-meshheading:19584291-Cell Line, Tumor,
pubmed-meshheading:19584291-Cell Proliferation,
pubmed-meshheading:19584291-Cell Survival,
pubmed-meshheading:19584291-Dose-Response Relationship, Drug,
pubmed-meshheading:19584291-Down-Regulation,
pubmed-meshheading:19584291-Forskolin,
pubmed-meshheading:19584291-GATA6 Transcription Factor,
pubmed-meshheading:19584291-Humans,
pubmed-meshheading:19584291-Hydrocortisone,
pubmed-meshheading:19584291-Insulin-Like Growth Factor I,
pubmed-meshheading:19584291-Phosphorylation,
pubmed-meshheading:19584291-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19584291-Recombinant Proteins,
pubmed-meshheading:19584291-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19584291-Steroid 17-alpha-Hydroxylase,
pubmed-meshheading:19584291-Time Factors,
pubmed-meshheading:19584291-Tretinoin,
pubmed-meshheading:19584291-Tumor Cells, Cultured
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pubmed:year |
2009
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pubmed:articleTitle |
Bone morphogenetic proteins 2 and 5 are down-regulated in adrenocortical carcinoma and modulate adrenal cell proliferation and steroidogenesis.
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pubmed:affiliation |
Departments of Medicine, University Hospital Innenstadt, Ludwig Maximilians University, Munich, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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