Linked Life Data

17066438

Source:http://linkedlifedata.com/resource/pubmed/id/17066438

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-12-4
pubmed:abstractText
Previous in vitro studies demonstrated that bioactive androgen 5alpha-dihydrotestosterone (DHT) exerted antiproliferative effects through an interaction with androgen receptor (AR) in breast carcinoma cells. However, AR status has not been examined in association with DHT concentration in breast carcinoma tissues, and significance of androgenic actions remains unclear in breast carcinomas. Therefore, in our study, we first examined intratumoral DHT concentrations in 38 breast carcinoma tissues using liquid chromatography/electrospray tandem mass spectrometry. Intratumoral DHT concentration was positively associated with 5alpha-reductase type 1 (5alphaRed1), and negatively correlated with aromatase. We then examined clinical significance of AR and 5alphaRed1 status in 115 breast carcinoma tissues by immunohistochemistry. Breast carcinomas positive for both AR and 5alphaRed1 were inversely associated with tumor size or Ki-67. These patients showed significant associations with a decreased risk of recurrence and improved prognosis for overall survival, and the AR / 5alphaRed1 status was demonstrated an independent prognostic factor. Moreover, we examined possible regulation of DHT production by aromatase in in vitro studies. DHT synthesis from androstenedione in MCF-7 cells was significantly inhibited by coculture with aromatase-positive stromal cells, which was significantly reversed by addition of aromatase inhibitor exemestane. These results suggest that intratumoral DHT concentration is mainly determined by 5alphaRed1 and aromatase in breast carcinoma tissues, and antiproliferative effect of DHT may primarily occur in the cases positive for both AR and 5alphaRed1. Aromatase inhibitors may be more effective in these patients, possibly due to increasing local DHT concentration with estrogen deprivation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
(c) 2006 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
285-91
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17066438-3-Oxo-5-alpha-Steroid 4-Dehydrogenase, pubmed-meshheading:17066438-Adult, pubmed-meshheading:17066438-Aged, pubmed-meshheading:17066438-Aged, 80 and over, pubmed-meshheading:17066438-Androgens, pubmed-meshheading:17066438-Aromatase, pubmed-meshheading:17066438-Aromatase Inhibitors, pubmed-meshheading:17066438-Breast Neoplasms, pubmed-meshheading:17066438-Carcinoma, Ductal, Breast, pubmed-meshheading:17066438-Chromatography, Liquid, pubmed-meshheading:17066438-Coculture Techniques, pubmed-meshheading:17066438-Dihydrotestosterone, pubmed-meshheading:17066438-Female, pubmed-meshheading:17066438-Humans, pubmed-meshheading:17066438-Immunohistochemistry, pubmed-meshheading:17066438-Ki-67 Antigen, pubmed-meshheading:17066438-Middle Aged, pubmed-meshheading:17066438-Receptors, Androgen, pubmed-meshheading:17066438-Tandem Mass Spectrometry, pubmed-meshheading:17066438-Tumor Cells, Cultured
pubmed:year
2007
pubmed:articleTitle
5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production.
pubmed:affiliation
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. t-suzuki@patholo2.med.tohoku.ac.jp
pubmed:publicationType
Journal Article