Cocchiola Rossana, Romaniello Donatella, Grillo Caterina, Altieri Fabio, Liberti Marcello, Magliocca Fabio Massimo, Chichiarelli Silvia, Marrocco Ilaria, Borgoni Giuseppe, Perugia Giacomo, Eufemi Margherita
Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
Istituto Pasteur, Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, Rome, Italy.
Oncotarget. 2017 Jun 27;8(26):42560-42570. doi: 10.18632/oncotarget.17245.
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.
前列腺癌（PCa）是一种复杂的异质性疾病。雄激素受体（AR）和信号转导与转录激活因子3（STAT3）可能是前列腺癌治疗的有效靶点。STAT3是一种细胞质潜伏转录因子，是多种致癌信号通路的枢纽蛋白，可上调许多参与肿瘤细胞增殖、血管生成、转移和细胞存活的基因的表达。STAT3的活性可通过几种翻译后修饰（PTM）来调节，这些修饰反映了特定的细胞状态，可能与前列腺癌的发生和发展有关。这项工作的目的是分析不同肿瘤阶段的STAT3翻译后修饰及其与STAT3细胞功能的关系。为此，对65例经福尔马林固定石蜡包埋（FFPE）的前列腺切除术标本进行了免疫印迹、免疫荧光染色和RT-PCR分析，这些标本根据不同的Gleason评分进行分类。所有实验均在配对的非肿瘤组织和肿瘤组织中进行。获得的数据显示，在所分析的肿瘤分级中，STAT3的翻译后修饰谱不同，这与特定STAT3相互作用蛋白的数量和分布差异以及STAT3靶基因的表达有关。这些结果突出了翻译后修饰作为一种额外的生物标志物对于准确评估前列腺癌分期和优化该疾病治疗的重要性。
