Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis.

Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis.
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DOI:
10.1038/bjc.2014.201
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发表时间:
2014-05-13
影响因子:
8.8
通讯作者:
Tang, D.
Tang, D.
中科院分区:
医学1区
文献类型:
--
作者:
Yan, J.;De Melo, J.;Cutz, J-C;Aziz, T.;Tang, D.

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越来越多的证据表明,醛脱氢(ALDH)在人类癌症类型中具有高水平的活性,部分原因是它与癌症干细胞有关。尽管ALDH1A1和ALDH7A1亚型被报道与前列腺肿瘤发生相关,但其他ALDH亚型是否与前列腺癌(PC)相关尚不清楚。分析了ALDH3A1在不同PC细胞系中的表达。异种移植肿瘤和54例原发性和转移性PC肿瘤采用免疫组化染色检测ALDH3A1表达。与非干细胞相比,在du145来源的PC干细胞(PCSCs)中观察到ALDH3A1的强烈上调。与源自DU145细胞的肿瘤相比,DU145 PCSCs产生的异种移植物肿瘤具有更高级的特征,前者中检测到更高水平的ALDH3A1;与局部异种移植物肿瘤相比,DU145细胞源性肺转移中ALDH3A1显著升高。此外,虽然在前列腺中未观察到ALDH3A1,但ALDH3A1在PIN中明显存在,并在癌中进一步增加。与配对的局部癌相比,ALDH3A1在淋巴结转移瘤中表达上调;ALDH3A1在骨转移性PC中的存在也得到证实。我们在此报告ALDH3A1与PC进展的关系。
Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated with prostate cancer (PC) remains unclear. ALDH3A1 expression was analysed in various PC cell lines. Xenograft tumours and 54 primary and metastatic PC tumours were stained using immunohistochemistry for ALDH3A1 expression. In comparison with the non-stem counterparts, a robust upregulation of ALDH3A1 was observed in DU145-derived PC stem cells (PCSCs). As DU145 PCSCs produced xenograft tumours with more advanced features compared with those derived from DU145 cells, higher levels of ALDH3A1 were detected in the former; a dramatic elevation of ALDH3A1 occurred in DU145 cell-derived lung metastasis compared with local xenograft tumours. Furthermore, while ALDH3A1 was not observed in prostate glands, ALDH3A1 was clearly present in PIN, and further increased in carcinomas. In comparison with the paired local carcinomas, ALDH3A1 was upregulated in lymph node metastatic tumours; the presence of ALDH3A1 in bone metastatic PC was also demonstrated. We report here the association of ALDH3A1 with PC progression.
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