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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1999-2-25
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pubmed:abstractText |
In the present study, we have investigated the expression of endothelin 1 (ET-1) and the ET(A) receptor (ET(A)R) and ET(B) receptor (ET(B)R) in primary (n = 30) and metastatic (n = 8) ovarian carcinomas and their involvement in tumor growth. By reverse transcription-PCR and Northern blot analysis, we detected ET-1 mRNA in 90% of primary and 100% of metastatic ovarian carcinomas. ET-1 mRNA expression was significantly higher in tumors than in normal ovarian tissues (n = 12; P < 0.01). ET(A)R mRNA was also detected in 84% of the carcinomas examined, whereas ET(B)R mRNA was expressed in 50% of the tumors. The in vivo presence of mature ET-1 and ET(A)R was confirmed by immunohistochemistry, demonstrating a higher expression in primary and metastatic cells. Ten primary cultures of ovarian tumors secreted ET-1 and were positive for ET-1 and ET(A)R mRNA, whereas only 40% expressed ET(B)R mRNA. Radioligand binding studies showed that ET-1-producing cells also expressed functional ET(A)R, whereas no specific ET(B)R could be demonstrated. ET-1 stimulated dose-dependent [3H]thymidine incorporation and enhanced the mitogenic effect of epidermal growth factor. The ET(A)R-selective antagonist BQ 123 strongly inhibited ET-1-stimulated growth and substantially reduced the basal growth rate of unstimulated cells, whereas the ET(B)R-selective antagonist BQ 788 had no effect. In conclusion, the present data demonstrate a novel mechanism in the growth control of ovarian carcinoma in vivo mediated by the ET-1 autocrine loop that selectively occurs via the ET(A)R.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin,
http://linkedlifedata.com/resource/pubmed/chemical/cyclo(Trp-Asp-Pro-Val-Leu)
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
59
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
720-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9973223-Adult,
pubmed-meshheading:9973223-Aged,
pubmed-meshheading:9973223-Blotting, Northern,
pubmed-meshheading:9973223-Cell Division,
pubmed-meshheading:9973223-Endothelin-1,
pubmed-meshheading:9973223-Female,
pubmed-meshheading:9973223-Humans,
pubmed-meshheading:9973223-Middle Aged,
pubmed-meshheading:9973223-Ovarian Neoplasms,
pubmed-meshheading:9973223-Peptides, Cyclic,
pubmed-meshheading:9973223-RNA, Messenger,
pubmed-meshheading:9973223-Receptor, Endothelin A,
pubmed-meshheading:9973223-Receptor, Endothelin B,
pubmed-meshheading:9973223-Receptors, Endothelin,
pubmed-meshheading:9973223-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:9973223-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Expression of endothelin 1 and endothelin A receptor in ovarian carcinoma: evidence for an autocrine role in tumor growth.
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pubmed:affiliation |
Laboratory of Molecular Pathology, Regina Elena Cancer Institute, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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