Increased expression of bHLH transcription factor E2A (TCF3) in prostate cancer promotes proliferation and confers resistance to doxorubicin induced apoptosis.
Increased expression of bHLH transcription factor E2A (TCF3) in prostate cancer promotes proliferation and confers resistance to doxorubicin induced apoptosis.
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DOI：
10.1016/j.bbrc.2012.04.126
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发表时间：
2012-05-25
影响因子：
3.1
通讯作者：
Chaudhary J
中科院分区：
文献类型：
--
作者：
Patel D;Chaudhary J
E2 A（TCF 3）是一种多功能碱性螺旋环螺旋（bHLH）转录因子。E2 A通过与细胞特异性bHLH蛋白的同源或异源二聚化来调节靶基因的转录。通常，E2 A促进细胞分化，在正常细胞和癌细胞系中充当细胞增殖的负调节剂，并且是正常B细胞发育所需的。鉴于E2 A调节/影响的多种生物学途径，对其在癌症中的表达知之甚少。在这项研究中，我们研究了E2 A在前列腺癌中的表达。出乎意料的是，E2 A免疫组织化学显示与正常前列腺相比，前列腺癌中E2 A表达增加。前列腺癌细胞DU 145和PC 3中E2 A的沉默导致G1期阻滞导致增殖显著减少，这部分是由CDKN 1A（p21）增加和Id 1、Id 3和c-myc减少介导的。前列腺癌细胞系中的E2 A沉默也导致由于线粒体通透性增加和半胱天冬酶3/7活化而增加的细胞凋亡。此外，E2 A的沉默增加了对阿霉素诱导的细胞凋亡的敏感性。基于我们的研究结果，我们提出E2 A可能是前列腺癌中高表达的Id 1和c-Myc的上游调节因子。这些结果首次证明E2 A实际上至少在前列腺癌中可以作为肿瘤促进剂。
E2A (TCF3) is a multifunctional basic helix loop helix (bHLH), transcription factor. E2A regulates transcription of target genes by homo- or heterodimerization with cell specific bHLH proteins. In general, E2A promotes cell differentiation, acts as a negative regulator of cell proliferation in normal cells and cancer cell lines and is required for normal B-cell development. Given the diverse biological pathways regulated/ influenced by E2A little is known about its expression in cancer. In this study we investigated the expression of E2A in prostate cancer. Unexpectedly, E2A immuno-histochemistry demonstrated increased E2A expression in prostate cancer as compared to normal prostate. Silencing of E2A in prostate cancer cells DU145 and PC3 led to a significant reduction in proliferation due to G1 arrest that was in part mediated by increased CDKN1A(p21) and decreased Id1, Id3 and c-myc. E2A silencing in prostate cancer cell lines also resulted in increased apoptosis due to increased mitochondrial permeability and caspase 3/7 activation. Moreover, silencing of E2A increased sensitivity to doxorubicin induced apoptosis. Based on our results, we propose that E2A could be an upstream regulator of Id1 and c-Myc which are highly expressed in prostate cancer. These results for the first time demonstrate that E2A could in fact acts as a tumor promoter at least in prostate cancer.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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影响因子：
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