Please use this identifier to cite or link to this item: https://doi.org/10.1677/ERC-10-0022
DC FieldValue
dc.titleDifferential expression of steroid 5α-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer
dc.contributor.authorDas, K.
dc.contributor.authorLorena, P.D.N.
dc.contributor.authorNg, L.K.
dc.contributor.authorLim, D.
dc.contributor.authorShen, L.
dc.contributor.authorSiow, W.Y.
dc.contributor.authorTeh, M.
dc.contributor.authorReichardt, J.K.V.
dc.contributor.authorSalto-Tellez, M.
dc.date.accessioned2014-05-20T02:29:10Z
dc.date.available2014-05-20T02:29:10Z
dc.date.issued2010-09
dc.identifier.citationDas, K., Lorena, P.D.N., Ng, L.K., Lim, D., Shen, L., Siow, W.Y., Teh, M., Reichardt, J.K.V., Salto-Tellez, M. (2010-09). Differential expression of steroid 5α-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer. Endocrine-Related Cancer 17 (3) : 757-770. ScholarBank@NUS Repository. https://doi.org/10.1677/ERC-10-0022
dc.identifier.issn13510088
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/53418
dc.description.abstractThe biological role of steroid 5a-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor β 1 (TGFB1), endothelin (EDN1), TGFα (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 μM). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors. © 2010 Society for Endocrinology.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1677/ERC-10-0022
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentPATHOLOGY
dc.description.doi10.1677/ERC-10-0022
dc.description.sourcetitleEndocrine-Related Cancer
dc.description.volume17
dc.description.issue3
dc.description.page757-770
dc.description.codenERCAE
dc.identifier.isiut000282445100023
Appears in Collections:Staff Publications

Show simple item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

20
checked on Nov 26, 2021

WEB OF SCIENCETM
Citations

20
checked on Nov 18, 2021

Page view(s)

134
checked on Nov 18, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.