Activator protein 2alpha transcription factor expression is associated with luminal differentiation and is lost in prostate cancer.
Activator protein 2alpha transcription factor expression is associated with luminal differentiation and is lost in prostate cancer.
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发表时间：
2001-12
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通讯作者：
M. Ruiz;P. Troncoso;C. Bruns;M. Bar‐eli
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作者：
M. Ruiz;P. Troncoso;C. Bruns;M. Bar‐eli
前列腺癌进展与E-cadherin、p21/WAF 1、MMP-2、VEGF和IGF结合蛋白3和5等基因的失调有关，所有这些基因都是转录因子激活蛋白2 α（AP-2 α）的靶基因。因此，我们假设前列腺癌的发生/进展与AP-2 α表达的变化有关。实验设计我们使用免疫荧光染色来评估AP-2 α在正常、良性和恶性人前列腺组织中的存在，并将其表达与肿瘤分级和分期相关联。结果AP-2 α在正常前列腺上皮中表达，而在30例不同Gleason评分的前列腺癌组织中均不表达。此外，AP-2 α蛋白存在于管腔细胞层中，但不存在于正常上皮的基底细胞层中，这表明前列腺癌标本中AP-2 α染色的丧失不是由于缺乏AP-2 α表达细胞。进一步分析表明，AP-2 α存在于2（40%）的5萎缩正常上皮，4（24%）的17例良性前列腺增生，2（13%）的13例高级别前列腺上皮内瘤变。在LNCaP、LNCaP-LN 3和PC 3 M-LN 4细胞系中也观察到AP-2 α表达的丧失或减少。结论：我们的数据表明，AP-2 α表达与正常的管腔分化有关，AP-2 α表达的缺失发生在前列腺癌发展的早期。AP-2 α的缺失可能导致通常调节细胞生长和分化的AP-2 α靶基因的失调。
PURPOSE Prostate cancer progression is associated with deregulation of genes like E-cadherin, p21/WAF1, MMP-2, VEGF, and IGF-binding protein, 3 and 5, all of which are target genes for the transcription factor activator protein 2alpha (AP-2alpha). We, therefore, hypothesize that the development/progression of prostate cancer is associated with changes in the expression of AP-2alpha. EXPERIMENTAL DESIGN We used immunofluorescent staining to assess the presence of AP-2alpha in normal, benign, and malignant human prostate tissues and to correlate its expression with tumor grade and stage. RESULTS We found that although AP-2alpha was expressed in normal prostate epithelium, it was not expressed in 30 prostate cancer specimens of different Gleason scores. Moreover, AP-2alpha protein was present in the luminal cell layer but not in the basal cell layer of the normal epithelium, which indicated that the loss of AP-2alpha staining in the prostate cancer specimens was not attributable to a lack of AP-2alpha-expressing cells. Further analysis demonstrated the presence of AP-2alpha in 2 (40%) of 5 atrophic normal epithelium, in 4 (24%) of 17 cases of benign prostatic hyperplasia, and in 2 (13%) of 13 cases of high-grade prostatic intraepithelial neoplasia. Loss or reduction in AP-2alpha expression was also observed in LNCaP, LNCaP-LN3, and PC3M-LN4 cell lines. CONCLUSIONS Our data demonstrate that AP-2alpha expression is associated with normal luminal differentiation and that a loss of AP-2alpha expression occurs early in the development of prostate adenocarcinoma. Loss of AP-2alpha may lead to deregulation in AP-2alpha target genes that normally regulate cellular growth and differentiation.