Activation of Androgen Receptor in Prostate Cancer: Role of Protein Kinase A and Extracellular Signal-regulated Kinases

機(jī)譯：前列腺癌中雄激素受體的激活 - 蛋白激酶A和細(xì)胞外信號調(diào)節(jié)激酶的作用

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The androgen receptor (AR) is a ligand-controlled transcription factor feat is required for normal development of the prostate. It is expressed in both A-dependent and -independent prostate cancer (PCA) cells. Emerging data suggest AR regulates growth of PCA cells even in the absence of As, implying it is activated by factors other than As. Herein, we show that stimulation of A-dependent PCA LNCaP cells with reagents that promote accumulation of cyclic adenosine monophosphate (cAMP) leads to protein kinase A (PKA)-dependent activation of AR. Importantly, dihydrotestosterone (DHT)-regulated activation of AR also required PKA. Stimulation with epidermal growth factor, that robustly activates extracellular signal-regulated kinase pathway, did not promote activation of AR. These data establish a critical role for PKA in AR activation and suggest it may contribute to the growth of A-independent prostate tumors.

機(jī)譯：雄激素受體（Ar）是一種配體控制的轉(zhuǎn)錄因子壯舉是前列腺正常發(fā)展所必需的。它在依賴于依賴性和依賴性前列腺癌（PCA）細(xì)胞中表達(dá)。新興數(shù)據(jù)表明AR即使在沒有AS的情況下，也調(diào)節(jié)PCA細(xì)胞的生長，這意味著它被除法以外的因素激活。在此，我們表明，刺激具有試劑的依賴性PCA LNCAP細(xì)胞，所述試劑促進(jìn)環(huán)狀腺苷一磷酸酯（CAMP）的積累導(dǎo)致蛋白激酶A（PKA） - 依賴性活化。重要的是，二氫酮（DHT）-Regulated的AR活化也需要PKA。刺激表皮生長因子，魯棒地激活細(xì)胞外信號調(diào)節(jié)激酶途徑，未促進(jìn)AR的激活。這些數(shù)據(jù)在AR激活中為PKA建立了關(guān)鍵作用，并表明它可能有助于患有無關(guān)的前列腺腫瘤的生長。

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《International Symposium on Hormonal Carcinogenesis》|2005年||共7頁
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Yehia Daaka; Elizabeth Kasbohm; Charles Yowel;
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中圖分類腫瘤病理生理學(xué);
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1. The Amino-terminal Domain of the Androgen Receptor Co-opts Extracellular Signal-regulated Kinase (ERK) Docking Sites in ELK1 Protein to Induce Sustained Gene Activation That Supports Prostate Cancer Cell Growth [J] . Rayna Rosati, Mugdha Patki, Venkatesh Chari, The Journal of biological chemistry . 2016,第50期

機(jī)譯：雄激素受體的氨基末端結(jié)構(gòu)域在ELK1蛋白中共溶劑腸道信號調(diào)節(jié)的激酶（ERK）對接位點(diǎn)，以誘導(dǎo)支持前列腺癌細(xì)胞生長的持續(xù)基因活化
2. Vasoactive intestinal peptide transactivates the androgen receptor through a protein kinase A-dependent extracellular signal-regulated kinase pathway in prostate cancer LNCaP cells. [J] . Xie Y, Wolff DW, Lin MF, Molecular pharmacology. . 2007,第1期

機(jī)譯：在前列腺癌LNCaP細(xì)胞中，血管活性腸肽通過蛋白激酶A依賴性細(xì)胞外信號調(diào)節(jié)激酶途徑使雄激素受體反式激活。
3. E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. [J] . Muramoto K, Goto M, Inoue Y, The Journal of Pharmacology and Experimental Therapeutics: Official Publication of the American Society for Pharmacology and Experimental Therapeutics . 2010,第1期

機(jī)譯：E6201，一種有絲分裂原激活的蛋白激酶/細(xì)胞外信號調(diào)節(jié)激酶激酶-1和有絲分裂原激活的蛋白激酶/細(xì)胞外信號調(diào)節(jié)激酶激酶激酶-1的新型激酶抑制劑：通過局部給藥對皮膚炎癥反應(yīng)的體內(nèi)作用。
4. Activation of Androgen Receptor in Prostate Cancer: Role of Protein Kinase A and Extracellular Signal-regulated Kinases [C] . Yehia Daaka, Elizabeth Kasbohm, Charles Yowel International Symposium on Hormonal Carcinogenesis . 2005

機(jī)譯：前列腺癌中雄激素受體的激活 - 蛋白激酶A和細(xì)胞外信號調(diào)節(jié)激酶的作用
5. RAF-1 kinase inhibitor protein-mediated cholecystokinin-2 receptor desensitization and extracellular signal-regulated kinase activation. [D] . Park, Jeseong. 2009

機(jī)譯：RAF-1激酶抑制劑蛋白介導(dǎo)的膽囊收縮素2受體脫敏和細(xì)胞外信號調(diào)節(jié)激酶激活。
6. The Amino-terminal Domain of the Androgen Receptor Co-opts Extracellular Signal-regulated Kinase (ERK) Docking Sites in ELK1 Protein to Induce Sustained Gene Activation That Supports Prostate Cancer Cell Growth [O] . Rayna Rosati, Mugdha Patki, Venkatesh Chari, 2016

機(jī)譯：雄激素受體的氨基末端域在ELK1蛋白中選擇細(xì)胞外信號調(diào)節(jié)激酶（ERK）?？课稽c(diǎn)以誘導(dǎo)支持前列腺癌細(xì)胞生長的持續(xù)基因激活。
7. The amino-terminal domain of the androgen receptor co-opts extracellular signal-regulated kinase (ERK) docking sites in ELK1 protein to induce sustained gene activation that supports prostate cancer cell growth [O] . Rosati, Rayna, Patki, Mugdha, Chari, Venkatesh, 2016

機(jī)譯：雄激素受體的氨基末端結(jié)構(gòu)域在ELK1蛋白中共選擇細(xì)胞外信號調(diào)節(jié)激酶（ERK）停靠位點(diǎn)，以誘導(dǎo)持續(xù)的基因激活，從而支持前列腺癌細(xì)胞的生長

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Activation of Androgen Receptor in Prostate Cancer: Role of Protein Kinase A and Extracellular Signal-regulated Kinases

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