PAX2 oncogene negatively regulates the expression of the host defense peptide human beta defensin-1 in prostate cancer.
PAX2 oncogene negatively regulates the expression of the host defense peptide human beta defensin-1 in prostate cancer.
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PAX2致癌基因对前列腺癌中宿主防御肽人β防御的表达负面调节。
DOI：
10.1016/j.molimm.2008.11.004
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发表时间：
2009-03
影响因子：
3.6
通讯作者：
Donald CD
中科院分区：
文献类型：
--
作者：
Bose SK;Gibson W;Bullard RS;Donald CD
人β防御素-1（hBD 1）是免疫系统的一个组成部分，其连接先天性和适应性免疫应答。我们已经证明，hBD 1诱导前列腺癌细胞的快速细胞溶解，它也可能具有肿瘤抑制能力。此外，hBD 1表达的癌症特异性丧失频率很高，这进一步表明其在肿瘤进展中的潜在作用。然而，导致hBD 1表达丧失的因素尚不清楚。PAX 2是一种通常在早期发育期间表达的转录调节因子，已被认为是肾脏、前列腺癌、乳腺癌和卵巢癌中的癌基因。已知PAX 2在这些肿瘤细胞中的表达通过抑制涉及p53肿瘤抑制因子的细胞死亡途径介导细胞死亡的逃避。然而，我们已经证明PAX 2表达的敲低导致细胞死亡，而不依赖于p53状态，从而表明PAX 2负调控另外的细胞死亡途径。在这里，我们描述了一种新的途径，其中PAX 2抑制hBD 1的表达，通过结合的PAX 2同源结构域的hBD 1启动子。此外，PAX 2表达的敲低导致hBD 1的重新表达，并随后导致前列腺癌细胞死亡。这些发现首次证明PAX 2癌基因抑制hBD 1在癌症中的表达，并进一步暗示PAX 2作为前列腺癌治疗的新靶点。
Human beta defensin-1 (hBD1) is a component of the immune system which links the innate and adaptive immune responses. We have demonstrated that hBD1 induces rapid cytolysis of prostate cancer cells and that it may also possess tumor suppressive abilities. In addition, there is a high frequency of cancer-specific loss of hBD1 expression which further suggests its potential role in tumor progression. However, the factors responsible for the loss of hBD1 expression are not known. PAX2, a transcriptional regulator normally expressed during early development, has been implicated as an oncogene in carcinomas of the kidney, prostate, breast and ovary. It is known that expression of PAX2 in these tumor cells mediates the evasion of cell death through the suppression of cell death pathways involving the p53 tumor suppressor. However, we have demonstrated that knock-down of PAX2 expression results in cell death independent of p53 status, thus suggesting that additional cell death pathways are negatively regulated by PAX2. Here we describe a novel pathway in which PAX2 represses hBD1 expression through binding of the PAX2 homeodomain to the hBD1 promoter. Furthermore, knock-down of PAX2 expression results in the re-expression of hBD1, and subsequently prostate cancer cell death. These findings are the first to demonstrate that the PAX2 oncogene suppresses hBD1 expression in cancer and further implicate PAX2 as a novel therapeutic target for prostate cancer treatment.
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影响因子：
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