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2017 ; 17
(6
): ä Nephropedia Template TP
gab.com Text
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English Wikipedia
Proteomics analyses of prostate cancer cells reveal cellular pathways associated
with androgen resistance
#MMPMID28116790
Höti N
; Shah P
; Hu Y
; Yang S
; Zhang H
Proteomics
2017[Mar]; 17
(6
): ä PMID28116790
show ga
While significant advances have been made in the diagnosis and treatment of
prostate cancer, each year tens of thousands of men still die from prostate
cancer in the United States. Thus, greater understanding of cellular pathways and
molecular basis of prostate cancer progression in the development of androgen
resistance is needed to treat these lethal phenotypes. To dissect the mechanism
of androgen resistance, we utilize a proteomics approach to study the development
of androgen resistance in LNCaP prostate cancer cells. Our results showed the
predominant involvement of metabolic pathways that were elevated in androgen
resistance phenotype. We further found the amplification of PI3K/AKT pathway and
the overexpression of proteasome proteins while the mitochondrial oxidation
phosphorylation was severely hampered in castration-resistant LNCaP-95 cells
compared to LNCaP cells. Interestingly, we also found the induction of Dicer, a
cytoplasmic endoribonuclease microRNA regulator in the androgen-ablated LNCaP-95
prostate cancer cells. We verified some of these data by orthogonal methods
including Western blot analysis and in castrated animal xenograft studies. To our
knowledge, this is the first report showing induced expression of proteasome
proteins in androgen ablation prostate cancer cells. If validated in clinical
studies, the findings will have significant implications in understanding the
complexity of biochemical recurrence in prostate cancer.
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