Analysis of Differentially Expressed Genes in LNCaP Prostate Cancer Progression Model
Analysis of Differentially Expressed Genes in LNCaP Prostate Cancer Progression Model
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LNCaP前列腺癌进展模型中差异表达基因分析
DOI：
10.2164/jandrol.109.008748
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发表时间：
2011-03-01
影响因子：
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通讯作者：
Zhou, Jian-Guang
中科院分区：
文献类型：
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作者：
Xie, Bang-Xiang;Zhang, Hui;Zhou, Jian-Guang
建立LNCaP/C4-2人前列腺癌进展模型，模拟前列腺癌从雄激素依赖到雄激素非依赖、从未转移到转移的表型和基因变化。在这项研究中，使用Affymetrix公司的微阵列芯片进行了基因芯片的研究，以表征和比较LNCaP和C4-2的基因表达谱，这可能为调节前列腺癌进展的分子机制提供新的见解。在两次微阵列数据中，318个基因在LNCaP和C4-2中持续差异表达。根据它们的功能，差异表达的基因可以分为几个亚类，包括生长因子和信号转导因子、癌基因和肿瘤抑制因子、肿瘤特异性抗原、转录因子、转运蛋白以及参与侵袭、转移和代谢的因子。一些基因在前列腺癌进展过程中是新的和未被探索的，对后续研究有潜在的兴趣。通过逆转录-聚合酶链式反应(RT-PCR)和实时定量RT-PCR对芯片结果进行验证，从104个候选基因中筛选出76个差异表达基因。对这76个差异表达基因进行了表达模式分析，发现在LNCaP前列腺癌进展模型中，有一系列基因与前列腺癌进展呈正或负相关，并具有明显的前列腺细胞特异性。ELF5/ESE-2b和长链酰基辅酶A脱氢酶(ACADL)的表达与LNCaP、C4-2和C4-2B的恶性进展呈正相关，且主要在前列腺癌细胞中表达。功能评价显示ELF5/ESE-2b和ACADL的表达与前列腺癌细胞的恶性表型有关。因此，我们的微阵列数据可能为寻找与前列腺癌进展到雄激素非依赖性和转移相关的新基因提供线索，并为前列腺癌的诊断和治疗寻找新的靶点。
The LNCaP/C4-2 human prostate cancer progression model was established to mimic phenotypic and genotypic changes during prostate cancer development from androgen dependence to androgen independence, from nonmetastasis to metastasis. In this study, cDNA microarrays were performed using a microarray chip from Affymetrix to characterize and compare gene expression profiles in LNCaP and C4-2, which may provide novel insight into the molecular mechanism mediating prostate cancer progression. Three hundred eighteen genes consistently exhibited differential expression in LNCaP and C4-2 in 2-time microarray data. Based on their function, the differentially expressed genes can be grouped into several subcategories, including growth factors and signal transducers, oncogenes and tumor suppressors, tumor-specific antigens, transcriptional factors, transporters, and factors involved in invasion, metastasis, and metabolism. Some genes are novel and unexplored in prostate cancer progression and are of potential interest for follow-up investigation. Reverse transcription polymerase chain reaction (RT-PCR) and real-time RT-PCR were performed to corroborate the microarray results, and 76 differentially expressed genes were validated out of 104 candidates. Expression pattern analyses were performed in these 76 differentially expressed genes, and a series of genes was found to be positively or negatively correlated to prostate cancer progression in the LNCaP prostate cancer progression model and to possess predominant prostate cell specificity. ELF5/ESE-2b and long-chain acyl coenzyme A dehydrogenase (ACADL) expressions were found to be positively associated with malignant progression in LNCaP, C4-2, and C4-2B, and predominantly expressed in prostate cancer cells. Functional evaluation revealed that ELF5/ESE-2b and ACADL expressions contributed to the malignant phenotypes of prostate cancer cells. Accordingly, our microarray data may provide clues for finding novel genes involved in prostate cancer progression to androgen independent and metastasis, and shed light on finding new targets for diagnosis and therapy of prostate cancer.