Human pHyde is not a classical tumor suppressor gene in prostate cancer
Human pHyde is not a classical tumor suppressor gene in prostate cancer
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DOI：
10.1002/ijc.11278
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发表时间：
2003-09-20
影响因子：
6.4
通讯作者：
Visakorpi, T
中科院分区：
文献类型：
--
作者：
Porkka, KP;Nupponen, NN;Visakorpi, T
最近从大鼠前列腺中克隆了一个新的抑癌基因pHyde。大鼠基因已被证明在体外和体内都能抑制前列腺癌细胞增殖。然而，人pHyde在前列腺癌中的作用以前没有研究过。在这里，我们分析了人前列腺癌细胞系（LNCaP，DU145，PC-3，22RvI），异种移植物（LuCaP 23.1，3S，41，49，58，69，70和73）和临床前列腺癌的遗传改变和pHyde的表达。采用北方分析和实时荧光定量RT-PCR方法研究了pHyde在正常人组织和前列腺癌中的表达。它在分析的所有正常组织中普遍表达。尽管低分化癌中的表达显着（p = 0.007）低于高分化和中等分化癌，但良性前列腺增生、未经治疗的原发性和复发性激素难治性前列腺癌之间的表达水平没有差异（p = 0.607）。总的来说，在68个研究样本中，通过变性高效液相色谱（DHPLC）和测序检测到2个错义突变（接近3%）。通过荧光原位杂交（FISH），其中一个具有突变的样本也表现出基因拷贝的丢失。这是唯一一个在两个等位基因中都表现出遗传改变的样本，表明人类pHyde不是经典的前列腺肿瘤抑制基因。在一些肿瘤中发现的基因表达减少值得进一步研究。(C)2003 Wiley-Liss，Inc.
A novel putative tumor suppressor gene, pHyde, was recently cloned from rat prostate. The rat gene has been shown to inhibit prostate cancer cell proliferation both in vitro and in vivo. However, the role of human pHyde in prostate cancer has not been studied before. Here, we analyzed human prostate cancer cell lines (LNCaP, DU145, PC-3, 22RvI), xenografts (LuCaP 23.1, 3S, 41, 49, 58, 69, 70 and 73) and clinical prostate carcinomas for genetic alterations and expression of pHyde. The expression of pHyde in normal human tissues as well as in prostate cancer was studied by Northern analysis and real-time quantitative RT-PCR. It was ubiquitously expressed in all normal tissues analyzed. Although, the expression was significantly (p=0.007) lower in poorly differentiated than in well and moderately differentiated carcinomas, there were no differences in the expression levels between benign prostate hyperplasia, untreated primary and recurrent hormone-refractory prostate carcinomas (p=0.607). Altogether, missense mutations were detected in 2 out of 68 samples studied (similar to3%) by denaturing high-performance liquid chromatography (DHPLC) and sequencing. One of the samples with the mutation also exhibited a loss of a gene copy by fluorescence in situ hybridization (FISH). This was the only sample that exhibited a genetic alteration in both alleles, suggesting that the human pHyde is not a classical prostate tumor suppressor gene. The reduced expression of the gene found in some tumors warrant further studies. (C) 2003 Wiley-Liss, Inc.