Dataset Information

Proteomics analyses of prostate cancer cells reveal cellular pathways associated with androgen resistance.

ABSTRACT: 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.

SUBMITTER: Hoti N

PROVIDER: S-EPMC5516940 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteomics analyses of prostate cancer cells reveal cellular pathways associated with androgen resistance.

Höti Naseruddin N Shah Punit P Hu Yingwei Y Yang Shuang S Zhang Hui H

Proteomics 20170301 6

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 ...[more]

PMID: 28116790

Similar Datasets

Project description:Treatment of prostate cancer confronts resistance to androgen receptor (AR)-targeted therapies. AR-associated coregulators and chromatin proteins hold a great potential for novel therapy targets. Here, we employed a powerful chromatin-directed proteomics approach termed ChIP-SICAP to uncover the composition of chromatin protein network, the chromatome, around endogenous AR in castration resistant prostate cancer (CRPC) cells. In addition to several expected AR coregulators, the chromatome contained many nuclear proteins not previously associated with the AR. In the context of androgen signaling in CRPC cells, we further investigated the role of a known AR-associated protein, a chromatin remodeler SMARCA4 and that of SIM2, a transcription factor without a previous association with AR. To understand their role in chromatin accessibility and AR target gene expression, we integrated data from ChIP-seq, RNA-seq, ATAC-seq and functional experiments. Despite the wide co-occurrence of SMARCA4 and AR on chromatin, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, especially those involved in cell morphogenetic changes in epithelial-mesenchymal transition. The depletion also inhibited the CRPC cell growth, validating SMARCA4's functional role in CRPC cells. Although silencing of SIM2 reduced chromatin accessibility similarly, it affected the expression of a much larger group of androgen-regulated genes, including those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of CRPC cells and tumor size in chick embryo chorioallantoic membrane assay, further emphasizing the importance of SIM2 in CRPC cells and pointing to the functional relevance of this potential prostate cancer biomarker in CRPC cells. Overall, the chromatome of AR identified in this work is an important resource for the field focusing on this important drug target.

Dataset Information

Proteomics analyses of prostate cancer cells reveal cellular pathways associated with androgen resistance.

Publications

Proteomics analyses of prostate cancer cells reveal cellular pathways associated with androgen resistance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets