Loss of androgen receptor-dependent growth suppression by prostate cancer cells can occur independently from acquiring oncogenic addiction to androgen receptor signaling.

PloS One
Jason D'AntonioJohn T Isaacs

Abstract

The conversion of androgen receptor (AR) signaling as a mechanism of growth suppression of normal prostate epithelial cells to that of growth stimulation in prostate cancer cells is often associated with AR mutation, amplification and over-expression. Thus, down-regulation of AR signaling is commonly therapeutic for prostate cancer. The E006AA cell line was established from a hormone naïve, localized prostate cancer. E006AA cells are genetically aneuploid and grow equally well when xenografted into either intact or castrated male NOG but not nude mice. These cells exhibit: 1) X chromosome duplication and AR gene amplification, although paradoxically not coupled with increased AR expression, and 2) somatic, dominant-negative Serine-599-Glycine loss-of-function mutation within the dimerization surface of the DNA binding domain of the AR gene. No effect on the growth of E006AA cells is observed using targeted knockdown of endogenous mutant AR, ectopic expression of wild-type AR, or treatment with androgens or anti-androgens. E006AA cells represent a prototype for a newly identified subtype of prostate cancer cells that exhibit a dominant-negative AR loss-of-function in a hormonally naïve patient. Such loss-of-function eliminates A...Continue Reading

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Citations

Jun 21, 2014·International Journal of Biological Sciences·Shahriar KoochekpourKristopher Attwood
Aug 17, 2010·Asian Journal of Andrology·Shahriar Koochekpour
Aug 1, 2014·International Journal of Biological Sciences·Shahriar KoochekpourKristopher Attwood
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Jul 6, 2021·Expert Opinion on Drug Discovery·Elisabete Nascimento-GonçalvesPaula A Oliveira

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Methods Mentioned

BETA
xenograft
immunoprecipitation
Assay
Fluorescence
FACS
PCR
Co-IP
enzymatic shearing
fluorescence activated cell sorting
nuclear translocation

Software Mentioned

FISH View

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