Xie Bang-Xiang, Zhang Hui, Wang Jian, Pang Bo, Wu Rui-Qin, Qian Xiao-Long, Yu Lan, Li Shan-Hu, Shi Qing-Guo, Huang Cui-Fen, Zhou Jian-Guang
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
J Androl. 2011 Mar-Apr;32(2):170-82. doi: 10.2164/jandrol.109.008748. Epub 2010 Sep 23.
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.
建立LNCaP/C4-2人前列腺癌进展模型是为了模拟前列腺癌从雄激素依赖到雄激素非依赖、从非转移到转移过程中的表型和基因型变化。在本研究中，使用Affymetrix的微阵列芯片进行cDNA微阵列分析，以表征和比较LNCaP和C4-2中的基因表达谱，这可能为介导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，共有318个基因在LNCaP和C4-2中持续表现出差异表达。根据其功能，差异表达基因可分为几个亚类，包括生长因子和信号转导分子、癌基因和肿瘤抑制基因、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中是新的且未被探索的，具有后续研究的潜在价值。进行逆转录-聚合酶链反应（RT-PCR）和实时RT-PCR以证实微阵列结果，在104个候选基因中有76个差异表达基因得到验证。对这76个差异表达基因进行表达模式分析，发现一系列基因在LNCaP前列腺癌进展模型中与前列腺癌进展呈正相关或负相关，并具有主要的前列腺细胞特异性。发现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中的恶性进展呈正相关，且主要在前列腺癌细胞中表达。功能评估表明，ELF5/ESE-2b和ACADL的表达促成了前列腺癌细胞的恶性表型。因此，我们的微阵列数据可能为寻找参与前列腺癌向雄激素非依赖和转移进展的新基因提供线索，并为前列腺癌的诊断和治疗寻找新靶点提供思路。
