Unique patterns of molecular profiling between human prostate cancer LNCaP and PC‐3 cells

Dozmorov, Mikhail G.; Hurst, Robert E.; Culkin, Daniel J.; Kropp, Bradley P.; Frank, Mark Barton; Osban, Jeanette; Penning, T.M.; Lin, Hsueh Kung

doi:10.1002/pros.20960

Cited by 89 publications

(84 citation statements)

References 58 publications

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“…Besides morphological differences, the two cell lines have been shown to have marked differences in Androgen receptor, Prostate specific antigen, Glutamate carboxypeptidase, Kallikrein 2, Prostatic acid phosphate, and Spondin 2 levels. The levels of these proteins have been previously reported to be elevated in LNCaP cells (4,28). However, these studies either evaluated the transcriptional activity or the protein expression of the cells with little to no information about the post-translational mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation*

Shah

Wang

Yang

et al. 2015

Molecular & Cellular Proteomics

118

123

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Prostate cancer is the most common cancer among men in the U.S. and worldwide, and androgen-deprivation therapy remains the principal treatment for patients. Although a majority of patients initially respond to androgen-deprivation therapy, most will eventually develop castration resistance. An increased understanding of the mechanisms that underline the pathogenesis of castration resistance is therefore needed to develop novel therapeutics. LNCaP and PC3 prostate cancer cell lines are models for androgen-dependence and androgen-independence, respectively. Herein, we report the comparative analysis of these two prostate cancer cell lines using integrated global proteomics and glycoproteomics. Global proteome profiling of the cell lines using isobaric tags for relative and absolute quantitation (iTRAQ) labeling and two-dimensional (2D) liquid chromatography-tandem MS (LC-MS/MS) led to the quantification of 8063 proteins. To analyze the glycoproteins, glycosite-containing peptides were isolated from the same iTRAQ-labeled peptides from the cell lines using solid phase extraction followed by LC-MS/MS analysis. Among the 1810 unique N-linked glycosite-containing peptides from 653 identified N-glycoproteins, 176 glycoproteins were observed to be different between the two cell lines. A majority of the altered glycoproteins were also observed with changes in their global protein expression levels. However, alterations in 21 differentially expressed glycoproteins showed no change at the protein abundance level, indicating that the glycosylation site occupancy was different between the two cell lines. To determine the glycosylation heterogeneity at specific glycosylation sites, we further identified and quantified 1145 N-linked glycopeptides with attached glycans in the same iTRAQ-labeled samples. These intact glycopeptides contained 67 glycan compositions and showed increased fucosylation in PC3 cells in several of the examined glycosylation sites. The increase in fucosylation could be caused by the detected changes in enzymes belonging to the glycan biosynthesis pathways of protein fucosylation observed in our proteomic analysis. The altered protein fucosylation forms have great potential in aiding our understanding of castration resistance and may lead to the development of novel therapeutic approaches and specific detection strategies for prostate cancer. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation*

Shah

Wang

Yang

et al. 2015

Molecular & Cellular Proteomics

118

123

View full text Add to dashboard Cite

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“…LNCaP is an androgen-dependent prostate cancer cell line that express mutant full-length AR; while 22Rv1 is a model of CRPC that expresses full-length mutated AR (110KDa) and constitutively active AR splice variants (80KDa). [31][32][33][34] We first asked whether NDRG2 can be regulated by AR signaling. DHT or bicalutamide were applied to stimulate or inhibit AR signaling.…”

Section: Ndrg2 Is Regulated By Ar and Is Involved In The Ar Signalingmentioning

confidence: 99%

NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits the growth of androgen-dependent and castration-resistant prostate cancer

Chen

et al. 2015

Cancer Biology & Therapy

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“…It has been extensively used as a cell model for the study of prostate cancer and is generally assumed to model an advanced stage of prostate cancer (4). PC3 cells are resistant to numerous chemotherapy drugs and apoptosis inducers (5,6).…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin induces autophagic cell death in prostate cancer cells in vitro

Yuan

Peng

et al. 2015

Molecular Medicine Reports

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Abstract. Athough it is well known that apoptosis contributes to cancer cell death, the role of autophagy in cancer cell death has remained in dispute. Atorvastatin has been suggested to exhibit anti-cancer effects. The present study aimed to examine atorvastatin-induced autophagy-associated cell death and the autophagy-associated gene expression profile in the PC3 prostate carcinoma cell line. The atorvastatin-induced process of autophagy in PC3 cells was determined via evaluation of the cellular expression levels of autophagosomal marker light-chain-3 (LC3)-II, using immunoblotting and counting of green fluorescent protein (GFP)-LC3-transfected autophagic cells. Apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and an MTT assay was used to evaluate cell viability. Total RNA of PC3 cells was isolated for characterization of the gene expression profile following atorvastatin treatment. Atorvastatin treatment of PC3 cells for 24 h increased the expression of green fluorescent protein-LC3-II by >25%, and expression continued for >72 h, while apoptosis was not significantly induced within this time period. Four genes associated with the autophagy machinery were also significantly upregulated. In the presence of atorvastatin, autophagy may be unable to abrogate cell damage and may therefore contribute to cellular dysfunction, leading to autophagic/type II programmed cell death. In response to atorvastatin treatment, the expression of genes involved in autophagic mediating pathways may have a role in tumor suppression. IntroductionProstate cancer is the most frequently diagnosed non-cutaneous malignancy and the second leading cause of death due to cancer amongst males worldwide (1). Treatment options for localized disease include watchful waiting, surgery and radiotherapy (2). However, in terms of a definitive treatment, despite developments in systemic chemotherapy strategies, minimal improvements in the quality of life and overall survival have been achieved amongst patients with prostate cancer (3). The development of novel treatment strategies for patients with advanced metastatic prostate cancers remains a challenge.The PC3 human prostate cancer cell line [p53-and phosphatase and tensin homolog (PTEN)-] was established from a prostatic adenocarcinoma, which was metastatic to bone. It has been extensively used as a cell model for the study of prostate cancer and is generally assumed to model an advanced stage of prostate cancer (4). PC3 cells are resistant to numerous chemotherapy drugs and apoptosis inducers (5,6).At o r va s t a t i n, a 3 -hyd r ox y-3 -m e t hylg lu t a r yl (HMG)-coenzyme A reductase inhibitor, is among the widely prescribed drugs used to lower cholesterol and prevent cardiovascular diseases (7). In addition to its cholesterol-lowering effect, atorvastatin has pro-apoptotic and anti-metastatic effects on prostate cancer cells (8,9). Parikh et al (10) hypothesized that atorvastatin may induce autophagy-associated cell death in PC3 cells. However, the...

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Unique patterns of molecular profiling between human prostate cancer LNCaP and PC‐3 cells

Cited by 89 publications

References 58 publications

Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation*

Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation*

NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits the growth of androgen-dependent and castration-resistant prostate cancer

Atorvastatin induces autophagic cell death in prostate cancer cells in vitro

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