Accession Number : ADA626032


Title :   Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy


Descriptive Note : Annual rept. 29 Sep 2014-28 Sep 2015


Corporate Author : TULANE UNIV NEW ORLEANS LA


Personal Author(s) : Zhang, Haitao


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a626032.pdf


Report Date : Oct 2015


Pagination or Media Count : 34


Abstract : During the first reporting period, we have made significant progress in understanding the fundamental difference in nuclear translocation mechanism between full-length androgen receptor (AR-FL) and AR splice variants (AR-Vs). We found that the AR-FL is associated with the microtubule cytoskeleton and is transported by the microtubules prior to its nuclear translocation. On the other hand, AR-V7 and ARv567es have weak microtubule-binding activities and use a microtubule-independent mechanism for intracellular transport. Through a series of deletion analyses, we have mapped the microtubule-binding activity to two regions in the AR ligand-binding domain. In addition, we found that AR-V7 and ARv567es interfere with docetaxelmediated AR-FL cytoplasmic retention, possibly by forming heterodimers with AR-FL and decreasing its microtubule-binding activity. These findings provide evidence that constitutively active AR-Vs maintain the AR signaling axis by evading the inhibitory effects of microtubule-targeting agents, suggesting that these AR-Vs play a role in resistance to taxane chemotherapy.


Descriptors :   *CHEMOTHERAPY , ANDROGENS , CELLS(BIOLOGY) , PROSTATE CANCER , RECEPTOR SITES(PHYSIOLOGY)


Subject Categories : Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE