Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway.
Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway.
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DOI：
10.1038/bjc.2013.160
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发表时间：
2013-06-25
影响因子：
8.8
通讯作者：
Batra SK
中科院分区：
文献类型：
--
作者：
Pandey P;Seshacharyulu P;Das S;Rachagani S;Ponnusamy MP;Yan Y;Johansson SL;Datta K;Fong Lin M;Batra SK
蛋白磷酸酶2A（PP 2A）是一种去磷酸化酶，其缺失可导致前列腺癌（PCa）发病。本研究的目的是分析在前列腺癌进展过程中PP 2A全酶的各个亚基的转录和翻译表达模式。对雄激素依赖性（AD）和雄激素非依赖性（AI）PCa细胞以及良性和恶性前列腺组织进行所有三种PP 2A（支架、调节和催化）亚基的免疫组织化学（IHC）、蛋白质印迹和实时PCR。使用各种生物化学和细胞技术进行机制和功能研究。免疫组化结果显示，前列腺癌组织中PP 2A-A和-B′γ亚基的表达明显低于良性前列腺组织（P<0.001和P=0.0002）。PP 2A-C亚基在良、恶性组织中的表达差异无统计学意义。与在组织中观察到的表达模式相似，从低转移到高转移以及从AD到AI细胞系模型，PP 2 A-A和B′γ亚基的内源性水平被废除，而催化亚基表达没有任何变化。此外，使用体外研究，我们证明了PP 2A-A α支架亚基在抑制AKT、β-连环蛋白和FAK（粘着斑激酶）信号传导中具有作用。我们的结论是支架和PP 2A的调节亚基的表达的损失是负责其功能改变PCa发病过程中。
Protein phosphatase 2A (PP2A) is a dephosphorylating enzyme, loss of which can contribute to prostate cancer (PCa) pathogenesis. The aim of this study was to analyse the transcriptional and translational expression patterns of individual subunits of the PP2A holoenzyme during PCa progression. Immunohistochemistry (IHC), western blot, and real-time PCR was performed on androgen-dependent (AD) and androgen-independent (AI) PCa cells, and benign and malignant prostate tissues for all the three PP2A (scaffold, regulatory, and catalytic) subunits. Mechanistic and functional studies were performed using various biochemical and cellular techniques. Through immunohistochemical analysis we observed significantly reduced levels of PP2A-A and -B′γ subunits (P<0.001 and P=0.0002) in PCa specimens compared with benign prostate. Contemporarily, there was no significant difference in PP2A-C subunit expression between benign and malignant tissues. Similar to the expression pattern observed in tissues, the endogenous levels of PP2A-A and B′γ subunits were abrogated from the low metastatic to high metastatic and AD to AI cell line models, without any change in the catalytic subunit expression. Furthermore, using in vitro studies we demonstrated that PP2A-Aα scaffold subunit has a role in dampening AKT, β-catenin, and FAK (focal adhesion kinase) signalling. We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis.
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影响因子：
50.3
作者：
Chen, W;Possemato, R;Hahn, WC
通讯作者：
Hahn, WC
影响因子：
3.7
作者：
Longin, Sari;Zwaenepoel, Karen;Janssens, Veerle
通讯作者：
Janssens, Veerle
影响因子：
10.3
作者：
Hankey, BF;Feuer, EJ;Kaplan, RS
通讯作者：
Kaplan, RS
影响因子：
64.8
作者：
Cho, Uhn Soo;Xu, Wenqing
通讯作者：
Xu, Wenqing
影响因子：
--
作者：
Bononi A;Agnoletto C;De Marchi E;Marchi S;Patergnani S;Bonora M;Giorgi C;Missiroli S;Poletti F;Rimessi A;Pinton P
通讯作者：
Pinton P