دورية أكاديمية
Proteomic characterization of peroxisome proliferator‐activated receptor‐γ (PPARγ) overexpressing or silenced colorectal cancer cells unveils a novel protein network associated with an aggressive phenotype
العنوان: | Proteomic characterization of peroxisome proliferator‐activated receptor‐γ (PPARγ) overexpressing or silenced colorectal cancer cells unveils a novel protein network associated with an aggressive phenotype |
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المؤلفون: | Maria Rita Milone, Biagio Pucci, Tommaso Colangelo, Rita Lombardi, Federica Iannelli, Vittorio Colantuoni, Lina Sabatino, Alfredo Budillon |
المصدر: | Molecular Oncology, Vol 10, Iss 8, Pp 1344-1362 (2016) |
بيانات النشر: | Wiley, 2016. |
سنة النشر: | 2016 |
المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
مصطلحات موضوعية: | Peroxisome proliferator-activated receptor gamma, Colorectal cancer, Proteomics, Ingenuity pathway analysis, 2-D DIGE, Mass spectrometry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | Peroxisome proliferator‐activated receptor‐γ (PPARγ) is a transcription factor of the nuclear hormone receptor superfamily implicated in a wide range of processes, including tumorigenesis. Its role in colorectal cancer (CRC) is still debated; most reports support that PPARγ reduced expression is associated with poor prognosis. We employed 2‐Dimensional Differential InGel Electrophoresis (2‐D DIGE) followed by Liquid Chromatography (LC)‐tandem Mass Spectrometry (MS/MS) to identify differentially expressed proteins and the molecular pathways underlying PPARγ expression in CRC progression. We identified several differentially expressed proteins in HT29 and HCT116 CRC cells and derived clones either silenced or overexpressing PPARγ, respectively. In Ingenuity Pathway Analysis (IPA) they showed reciprocal relation with PPARγ and a strong relationship with networks linked to cell death, growth and survival. Interestingly, five of the identified proteins, ezrin (EZR), isoform C of prelamin‐A/C (LMNA), alpha‐enolase (ENOA), prohibitin (PHB) and RuvB‐like 2 (RUVBL2) were shared by the two cell models with opposite expression levels, suggesting a possible regulation by PPARγ. mRNA and western blot analysis were undertaken to obtain a technical validation and confirm the expression trend observed by 2‐D DIGE data. We associated EZR upregulation with increased cell surface localization in PPARγ‐overexpressing cells by flow cytometry and immunofluorescence staining. We also correlated EZR and PPARγ expression in our series of CRC specimens and the expression profiling of all five proteins levels in the publicly available colon cancer genomic data from Oncomine and Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) datasets. In summary, we identified a panel of proteins correlated with PPARγ expression that could be associated with CRC unveiling new pathways to be investigated for the selection of novel potential prognostic/predictive biomarkers and/or therapeutic targets. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1878-0261 1574-7891 |
Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
DOI: | 10.1016/j.molonc.2016.07.006 |
URL الوصول: | https://doaj.org/article/5ae5e0d1419249a9988f3822d21263f4 |
رقم الأكسشن: | edsdoj.5ae5e0d1419249a9988f3822d21263f4 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 18780261 15747891 |
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DOI: | 10.1016/j.molonc.2016.07.006 |