Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons
Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons
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DOI：
10.1038/sj.onc.1207297
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发表时间：
2004-03-04
期刊：
影响因子：
8
通讯作者：
Naaby-Hansen, S
中科院分区：
文献类型：
--
作者：
Nagano, K;Masters, JR;Naaby-Hansen, S
通过蛋白质组分析比较来自同一患者的正常细胞系和前列腺癌细胞系中的蛋白质表达和从头合成，并确定 INFα 和 INFgamma（INF = 干扰素）的作用。癌细胞中多种 INF 诱导蛋白的表达下调，包括 MxA、Nmi、PA28a 和 IFP53。 INFgamma 诱导癌细胞系中几乎两倍的蛋白质合成率增加或减少两倍以上。 INF 诱导转录的正调节因子 ISGF3gamma 在癌细胞中上调，而在正常细胞和癌细胞中受 INFα 和 INFgamma 负调节。此外，与正常细胞中的ISGF3gamma诱导相比，通过同时刺激EGF，癌细胞中INFgamma对ISGF3gamma的诱导作用更加增强。通过质谱分析总共鉴定出了 31 种差异调节蛋白，其中一些蛋白参与内质网 (ER) 中分子伴侣辅助的蛋白折叠或调节蛋白降解。我们的结果表明，ER 质量控制系统对蛋白质的排除、EGF 和 INF 诱导的信号通路之间的串扰以及 INF 诱导基因的调节在前列腺癌细胞中都发生了改变。促进生长的 PI3K/Akt 通路活性上调、Nmi 抑制以及 hnRNP-K 和 c-myc 蛋白过度表达的结合可能解释了为什么前列腺癌细胞对 INFgamma 的生长抑制作用更具抵抗力。
Protein expression and de novo synthesis in normal and prostate cancer cell lines derived from the same patient were compared by proteomic analysis, and the effects of INFalpha and INFgamma ( INF = interferon) determined. The expressions of several INF-inducible proteins, including MxA, Nmi, PA28a and IFP53, were downregulated in the cancer cells. INFgamma induced a more than twofold increase or decrease in the synthesis rates of almost twice as many proteins in the cancer cell line. The positive regulator of INF-induced transcription ISGF3gamma was upregulated in the cancer cells and inversely regulated by INFalpha and INFgamma in the normal and cancer cells. Moreover, ISGF3gamma's induction by INFgamma in the cancer cells was more enhanced by simultaneous stimulation with EGF, than its induction in the normal cells. In all, 31 differentially regulated proteins were identified by mass spectrometry analysis, several of which are involved in chaperone-assisted protein folding in the endoplasmic reticulum ( ER) or in regulated protein degradation. Our results suggest that the exclusion of proteins by the ER quality control system, crosstalk between the EGF- and INF-induced signalling pathways and the regulation of INF-inducible genes are all altered in the prostate cancer cells. The combination of upregulated activity in the growth-promoting PI3K/Akt pathway, suppression of Nmi and overexpression of hnRNP-K and c-myc proteins may explain why the prostate cancer cells were found to be more resistant to the growth inhibitory effects of INFgamma.