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- W280144949 abstract "Abstract : Previous analysis of the CWR22Rv1 relapsed androgen independent tumor line revealed that it expresses the full length androgen receptor (FL-AR) and an low molecular weight (LMW) that has a deletion of the C-terminal ligand binding domain (LBD). Calpain proteolysis removes the LBD generating a constitutively active molecule. Our studies showed that the LMW AR is present in some prostate tumors. Inhibition of calpain activity by calpain inhibitors in CWR22Rv1 cells prevents AR proteolysis. Calpain inhibition by calpepetin and the HIV protease inhibitors in the absence androgens promotes cell death in cell culture and animal xenograft studies. In Rv1 cells a 39aa insertional mutation of the AR sensitizes AR to calpain proteolysis, while in the related R1 cells the levels and activity of calpain are elevated. In R1 cells LMW AR expression is regulated by the ERK kinase. In studies that address the role of the LMW AR in transcription we found that two CWR22 derived cells lines have a very similar AR binding pattern. Surprisingly the gene expression profile of the two lines is very different and most importantly the cohort of androgen regulated genes is different in the two cell lines. This indicates that AR binding is not sufficient to drive androgen-dependent transcription, and that transcription is dependent on additional factors that are cell specific. An analysis of the LMW AR binding and gene regulation indicates that the LMW AR binds to a subset of sites that are bound by the FL-AR, indicating that the LMW-AR does not bind a distinct set of genes. Expression studies found that the LMW AR is not subject to regulation by Filamin A a AR co-repressor." @default.
- W280144949 created "2016-06-24" @default.
- W280144949 creator A5014332343 @default.
- W280144949 date "2009-11-01" @default.
- W280144949 modified "2023-09-28" @default.
- W280144949 title "Calpain-Dependent Proteolysis of the Androgen Receptor" @default.
- W280144949 doi "https://doi.org/10.21236/ada517269" @default.
- W280144949 hasPublicationYear "2009" @default.
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