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Göteborgs universitets publikationer

miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis

Författare och institution:
O. Larne (-); Z. Hagman (-); H. Lilja (-); A. Bjartell (-); Anders Edsjö (Institutionen för biomedicin, avdelningen för patologi); Y. Ceder (-)
Publicerad i:
Carcinogenesis, 36 ( 8 ) s. 858-866
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Androgen signalling through the androgen receptor (AR) is essential for prostate cancer initiation, progression and transformation to the lethal castration-resistant state. The aim of this study was to characterize the mechanisms by which miR-145 deregulation contribute to prostate cancer progression. The miR-145 levels, measured by quantitative reverse transcription-polymerase chain reaction, were found to inversely correlate with occurrence of metastases, survival and androgen deprivation therapy response in a well-characterized prostate cancer cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an inhibitory effect on the AR at both transcript and protein levels as well as its activity and downstream targets prostate-specific antigen (PSA), kallikrein-related peptidase 2 and TMPRSS2. The regulation was shown to be mediated by direct binding using Ago2-specific immunoprecipitation, but there was also indication of synergetic AR activation. These findings were verified in clinical prostate specimens by demonstrating inverse correlations between miR-145 and AR expression as well as serum PSA levels. In addition, miR-145 was found to regulate androgen-dependent cell growth in vitro. Our findings put forward novel possibilities of therapeutic intervention, as miR-145 potentially could decrease both the stem cells and the AR expressing bulk of the tumour and hence reduce the transformation to the deadly castration-resistant form of prostate cancer. © The Author 2015. Published by Oxford University Press. All rights reserved.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Cancer och onkologi
Postens nummer:
Posten skapad:
2015-11-24 09:56
Posten ändrad:
2015-11-24 09:57

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