Do Androgen Receptor Splice Variants Facilitate Growth of Bone Metastases
Technical Report,01 Sep 2015,31 Aug 2016
Baylor College of Medicine Houston United States
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Among the mechanisms for resistance to anti-androgen therapy is expression of constitutively active AR splice variants, which lack the carboxyl terminal hormone binding domain. The best characterized variant is AR-V7. Expression of this variant is especially prominent in bone metastases and the morbidity and mortality due to bone metastases is one of the most significant problems in the treatment of PCa. The role of variants in PCa is still contentious. We have used lentiviruses to make LNCaP and VCaP cell lines that express AR-V7 in response to doxycycline and have compared gene expression regulated by AR and AR-V7 in the LNCaP lineage. We found many differences between the two isoforms. One of the most striking was evidence of activation of Notch signaling by AR-V7. Notch signaling has been implicated in growth of bone metastases. We hypothesize that AR-V7 mediated induction of Notch signaling to promotes growth of bone metastases. Our initial studies show that AR-V7 induces a number of bone related genes, which may facilitate growth in a bone microenvironment.
- Medicine and Medical Research