کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5500965 | 1534623 | 2017 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of protein kinase C-related kinase (PRK) signalling by the TPα and TPβ isoforms of the human thromboxane A2 receptor: Implications for thromboxane- and androgen- dependent neoplastic and epigenetic responses in prostate cancer
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کلمات کلیدی
PDK-1RBDKallikreinNTDTxA2PRKCRPCWDR5H3K9ADTKLKPKNLysine-specific demethylaseTMPRSS2T-loophistone H3 lysine 9C-tailERKDHTCOXFBSLSDBCRMOFPSAPCA - PCASmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAAndrogen - آندروژنArachidonic acid - اسید آراشیدونیکEpigenetics - اپی ژنتیکchromatin immunoprecipitation - ایمن سازی کروماتینthromboxane - ترومبوکسیانTau - خود راamino-terminal domain - دامنه آمینو ترمینالADT, Androgen deprivation therapy - درمان محرومیت از آندروژنcarboxyl-terminal tail - دم کربوکسیل پایانیDihydrotestosterone - دی هیدروتستوسترونRho binding domain - رحم اتصالProstate cancer - سرطان پروستاتcastrate resistant prostate cancer - سرطان پروستات مقاوم در برابر کورتاژfetal bovine serum - سرم جنین گاوextracellular signal regulated protein kinase - سیگنال خارج سلولی پروتئین کیناز را تنظیم می کندandrogen response element - عنصر پاسخ آندروژنBiochemical recurrence - عود بیوشیمیاییARE - هستند3-phosphoinositide-dependent protein kinase-1 - وابسته به پروتئین کیناز-1 وابسته به 3-فسفوئوزیتیدprostate-specific antigen - پادگن مخصوص پروستاتtransmembrane protease serine 2 - پروتئاز ترانس مایع سریین 2Protein kinase - پروتئین کینازCHiP - چیپReceptor - گیرنده Androgen Receptor - گیرنده آندروژنی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The prostanoid thromboxane (TX) A2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA2/TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA2-TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC. Hence the aim of the current study was to investigate whether TXA2/TP-induced PRK activation can mimic and/or enhance AR-mediated cellular responses in the model androgen-responsive prostate adenocarcinoma LNCaP cell line. We reveal that TXA2/TP signalling can act as a neoplastic- and epigenetic-regulator, promoting and enhancing both AR-associated chromatin remodelling (H3Thr11 phosphorylation, WDR5 recruitment and acetylation of histone H4 at lysine 16) and AR-mediated transcriptional activation (e.g of the KLK3/prostate-specific antigen and TMPRSS2 genes) through mechanisms involving TPα/TPβ mediated-PRK1 and PRK2, but not PRK3, signalling complexes. Overall, these data demonstrate that TPα/TPβ can act as neoplastic and epigenetic regulators by mimicking and/or enhancing the actions of androgens within the prostate and provides further mechanistic insights into the role of the TXA2/TP signalling axis in PCa, including potentially in CRPC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1863, Issue 4, April 2017, Pages 838-856
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1863, Issue 4, April 2017, Pages 838-856
نویسندگان
Aine G. O'Sullivan, Eamon P. Mulvaney, B. Therese Kinsella,