Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.

Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.
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前列腺癌进展过程中基因表达谱的变化:与小鼠和人类肿瘤中的致瘤性和硒蛋白-P 下调的功能相关性。

DOI:
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发表时间:
2002
期刊:
影响因子:
11.2
通讯作者:
Jeffrey E. Green
Jeffrey E. Green
中科院分区:
医学1区
文献类型:
--
作者:
A. Calvo;N. Xiao;J. Kang;Carolyn J. M. Best;Isabel M Leiva;M. Emmert;C. Jorcyk;Jeffrey E. Green

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为了鉴定前列腺肿瘤进展过程中发生的分子变化,我们对一系列从C3(1)/Tag转基因小鼠中分离的处于肿瘤发生不同阶段的前列腺癌细胞系进行了表征。来自低级别和高级别前列腺上皮内瘤变、浸润性癌和肺转移的细胞系在细胞生长、致瘤性、侵袭性和血管生成方面表现出显著差异。对8700个特征的cDNA微阵列分析揭示了C3(1)/Tag-Pr细胞的致瘤性与调节细胞生长、血管生成和侵袭的基因表达水平的变化之间的相关性。在该体外系统中观察到的转录调控中的许多变化与人类前列腺癌以及其他类型的人类肿瘤中报道的那些相似。这种表达模式的分析还确定了可能参与前列腺肿瘤发生机制或作为前列腺癌的潜在生物标志物或治疗靶点的新基因。例子包括L1细胞粘附分子、转移相关基因(MTA-2)、Rab-25、肿瘤相关信号转导子-2(Trop-2)和硒蛋白-P(一种结合硒并防止氧化应激的基因)。在Pr细胞系模型中鉴定的许多基因已显示在人前列腺癌中改变。全面的微阵列数据提供了一个合理的基础,使用该模型系统的研究,其中特定基因或途径的改变是特别感兴趣的。硒蛋白-P的定量实时逆转录-PCR证明了该基因在人前列腺肿瘤、小鼠肿瘤和前列腺癌细胞系的一个子集中的转录物的类似下调。这项工作表明,在动物模型中的表达谱可能导致识别新的基因参与人类前列腺癌生物学。
To identify molecular changes that occur during prostate tumor progression, we have characterized a series of prostate cancer cell lines isolated at different stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and a lung metastasis exhibited significant differences in cell growth, tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700 features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr cells and changes in the expression levels of genes regulating cell growth, angiogenesis, and invasion. Many changes observed in transcriptional regulation in this in vitro system are similar to those reported for human prostate cancer, as well as other types of human tumors. This analysis of expression patterns has also identified novel genes that may be involved in mechanisms of prostate oncogenesis or serve as potential biomarkers or therapeutic targets for prostate cancer. Examples include the L1-cell adhesion molecule, metastasis-associated gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many genes identified in the Pr-cell line model have been shown to be altered in human prostate cancer. The comprehensive microarray data provides a rational basis for using this model system for studies where alterations of specific genes or pathways are of particular interest. Quantitative real-time reverse transcription-PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript of this gene in a subset of human prostate tumors, mouse tumors, and prostate carcinoma cell lines. This work demonstrates that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology.
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影响因子: 2.1
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发表时间: 2001
影响因子: 3.3
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发表时间: 1996-12-25
影响因子: 120.7
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