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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2011-5-26
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pubmed:abstractText |
Glucocorticoids (GC) have important anti-inflammatory and pro-apoptotic activities. Initially thought to be exclusively produced by the adrenal glands, there is now increasing evidence for extra-adrenal sources of GCs. We have previously shown that the intestinal epithelium produces immunoregulatory GCs and that intestinal steroidogenesis is regulated by the nuclear receptor liver receptor homolog-1 (LRH-1). As LRH-1 has been implicated in the development of colon cancer, we here investigated whether LRH-1 regulates GC synthesis in colorectal tumors and whether tumor-produced GCs suppress T-cell activation. Colorectal cancer cell lines and primary tumors were found to express steroidogenic enzymes and regulatory factors required for the de novo synthesis of cortisol. Both cell lines and primary tumors constitutively produced readily detectable levels of cortisol, as measured by radioimmunoassay, thin-layer chromatography and bioassay. Whereas overexpression of LRH-1 significantly increased the expression of steroidogenic enzymes and the synthesis of cortisol, downregulation or inhibition of LRH-1 effectively suppressed these processes, indicating an important role of LRH-1 in colorectal tumor GC synthesis. An immunoregulatory role of tumor-derived GCs could be further confirmed by demonstrating a suppression of T-cell activation. This study describes for the first time cortisol synthesis in a non-endocrine tumor in humans, and suggests that the synthesis of bioactive GCs in colon cancer cells may account as a novel mechanism of tumor immune escape.
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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/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol Side-Chain Cleavage...,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrocortisone,
http://linkedlifedata.com/resource/pubmed/chemical/NR5A2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid 11-beta-Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic acute regulatory...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1476-5594
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2411-9
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pubmed:meshHeading |
pubmed-meshheading:21258413-Animals,
pubmed-meshheading:21258413-Anti-Inflammatory Agents,
pubmed-meshheading:21258413-Apoptosis,
pubmed-meshheading:21258413-Caco-2 Cells,
pubmed-meshheading:21258413-Cholesterol Side-Chain Cleavage Enzyme,
pubmed-meshheading:21258413-Chromatography, Thin Layer,
pubmed-meshheading:21258413-Colonic Neoplasms,
pubmed-meshheading:21258413-Culture Media, Conditioned,
pubmed-meshheading:21258413-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21258413-Glucocorticoids,
pubmed-meshheading:21258413-HEK293 Cells,
pubmed-meshheading:21258413-HT29 Cells,
pubmed-meshheading:21258413-Humans,
pubmed-meshheading:21258413-Hydrocortisone,
pubmed-meshheading:21258413-Lymphocyte Activation,
pubmed-meshheading:21258413-Mice,
pubmed-meshheading:21258413-Mice, Inbred C57BL,
pubmed-meshheading:21258413-Phosphoproteins,
pubmed-meshheading:21258413-RNA Interference,
pubmed-meshheading:21258413-Radioimmunoassay,
pubmed-meshheading:21258413-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:21258413-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21258413-Spleen,
pubmed-meshheading:21258413-Steroid 11-beta-Hydroxylase,
pubmed-meshheading:21258413-T-Lymphocytes,
pubmed-meshheading:21258413-Thymus Gland
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pubmed:year |
2011
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pubmed:articleTitle |
Colon cancer cells produce immunoregulatory glucocorticoids.
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pubmed:affiliation |
Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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