Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
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DOI：
10.1016/j.yexmp.2014.09.012
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发表时间：
2014-12-01
影响因子：
3.6
通讯作者：
Marta Facchinetti, Maria
中科院分区：
文献类型：
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作者：
Carolina Andres, Nancy;Eugenia Fermento, Maria;Marta Facchinetti, Maria
血红素氧合酶-1（HO-1）的表达在结直肠癌（CRC）中被上调，但其在这种癌症类型中的作用尚未得到解决。本研究的目的是分析HO-1在人类侵袭性结直肠癌中的表达，评估其与临床和组织病理学参数的相关性，并研究该酶影响肿瘤进展的机制。我们证实HO-1在人类侵袭性结直肠癌中过度表达，并发现该酶的表达与较长的总生存时间相关。此外，我们在化学诱导的CRC动物模型中观察到总HO-1和核HO-1表达随着肿瘤进展而增加。我们的研究HO-1在CRC中的作用机制表明，该蛋白通过诱导细胞周期阻滞和凋亡降低细胞活力，重要的是，这些作用需要功能性p53肿瘤抑制蛋白。这种细胞活力的降低伴随着p21、p27和细胞周期蛋白D1水平的调节以及Akt和PKC途径的调节。总之，我们的研究结果表明HO-1的抗肿瘤作用，并指出p53状态在这种抗肿瘤活性的重要性。(C)2014爱思唯尔公司All rights reserved.
The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over-expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate an antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity. (C) 2014 Elsevier Inc. All rights reserved.