Analysis of STAT3 post-translational modifications (PTMs) in human prostate cancer with different Gleason Score
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Rossana Cocchiola1,2,5,*, Donatella Romaniello1,2,*, Caterina Grillo1,2, Fabio Altieri1,2, Marcello Liberti3, Fabio Massimo Magliocca4, Silvia Chichiarelli1,2, Ilaria Marrocco1,2, Giuseppe Borgoni3, Giacomo Perugia3,* and Margherita Eufemi1,2,*
1Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy
2Istituto Pasteur, Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, Rome, Italy
3Department of Gynecological-Obstretic Science and Urologic Sciences, Sapienza University of Rome, Rome, Italy
4Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
5Fondazione Enrico ed Enrica Sovena, Rome, Italy
*These authors contributed equally to this work
Margherita Eufemi, email: firstname.lastname@example.org
Keywords: STAT3, PTMs, signaling pathways, prostate cancer, biomarkers
Received: June 08, 2016 Accepted: April 05, 2017 Published: April 19, 2017
Prostate Cancer (PCa) is a complex and heterogeneous disease. The androgen receptor (AR) and the signal transducer and activator of transcription 3 (STAT3) could be effective targets for PCa therapy. STAT3, a cytoplasmatic latent transcription factor, is a hub protein for several oncogenic signalling pathways and up-regulates the expression of numerous genes involved in tumor cell proliferation, angiogenesis, metastasis and cell survival. STAT3 activity can be modulated by several Post-Translational Modifications (PTMs) which reflect particular cell conditions and may be implicated in PCa development and progression. The aim of this work was to analyze STAT3 PTMs at different tumor stages and their relationship with STAT3 cellular functions. For this purpose, sixty-five prostatectomy, Formalin-fixed paraffin-embedded (FFPE) specimens, classified with different Gleason Scores, were subjected to immunoblotting, immunofluorescence staining and RT-PCR analysis. All experiments were carried out in matched non-neoplastic and neoplastic tissues. Data obtained showed different STAT3 PTMs profiles among the analyzed tumor grades which correlate with differences in the amount and distribution of specific STAT3 interactors as well as the expression of STAT3 target genes. These results highlight the importance of PTMs as an additional biomarker for the exactly evaluation of the PCa stage and the optimal treatment of this disease.
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