不同转移潜能人肝癌细胞系的基因表达分析

目的：比较不同转移潜能人肝癌细胞系的基因表达谱,寻找与癌转移相关的基因表达改变。方法：采用基因芯片技术,比较遗传背景相同但转移力有明显差异的两个细胞系MHCC97－L和HCCLM3,分析其基因表达谱的差异。结果：在1626个候选基因中,筛选出25个差异表达基因。HCCLM3与MHCC97－L相比,表达上调的基因有8个,包括细胞增生基因E25、信号传导基因NKK6和免疫相关基因SP40,40等;下调的有17个,包括细胞周期调控基因Rb2、信号传导基因PKCβ2和错配修复基因hMSH2等。结论：肝癌转移是多基因作用的综合结果,筛选的基因对预测转移和抗转移干预措施可能有指导意义。     

趋化因子及其受体与肿瘤

趋化因子及其受体在肿瘤的发生、生长和转移等各个阶段都有复杂的网络性表达，研究表明趋化因子CXCL12及受体CXCR4介导乳腺癌、结肠癌、膀胱癌和前列腺癌等肿瘤的转移和发展，这为深入探讨肿瘤的发病及转移机制提供了新视角。现对近年来有关趋化因子及其受体与肿瘤之间的研究进展作一综述。     

趋化因子受体与肿瘤转移

目前认为肿瘤细胞转移和淋巴细胞迁移具有相似机制,但趋化因子及其受体参与肿瘤转移的机制尚未完全阐明。由于其在肿瘤细胞器官选择性转移中的重要作用,趋化因子受体有希望成为肿瘤治疗的靶标并具有预后价值。现综述趋化因子受体与肿瘤侵袭和转移的研究进展。     

趋化因子受体与肿瘤转移

目前认为肿瘤细胞转移和淋巴细胞迁移具有相似机制,但趋化因子及其受体参与肿瘤转移的机制尚未完全阐明。由于其在肿瘤细胞器官选择性转移中的重要作用,趋化因子受体有希望成为肿瘤治疗的靶标并具有预后价值。现综述趋化因子受体与肿瘤侵袭和转移的研究进展。     

趋化因子及其受体与肿瘤

趋化因子及其受体在肿瘤的发生、生长和转移等各个阶段都有复杂的网络性表达,研究表明趋化因子CXCL12及受体CXCR4介导乳腺癌、结肠癌、膀胱癌和前列腺癌等肿瘤的转移和发展,这为深入探讨肿瘤的发病及转移机制提供了新视角。现对近年来有关趋化因子及其受体与肿瘤之间的研究进展作一综述。     

趋化因子及受体在肝癌侵袭转移中的研究进展

近年来趋化因子及其受体领域已经受到广泛关注。它们是一个促炎多肽细胞因子的超家族,具有众多成员。趋化因子及其相应的受体在多种生理和病理过程中发挥着重要作用。研究表明,它们与肿瘤的血管生成、发生发展、侵袭转移及治疗预后都有着密切关系。文章就趋化因子及其受体在肝癌侵袭转移中的机制及其研究进展作一综述。     

趋化因子及其受体在肿瘤侵袭转移中的作用

近年来陆续发现了许多新的趋化因子和受体，研究发现趋化因子及其受体参与机体的多种生理和病理过程，并在肿瘤的侵袭转移中通过不同机制发挥着重要作用。本文对其进行简要综述。     

趋化因子与肿瘤侵袭转移

趋化因子是一类具有趋化作用的分泌型小分子蛋白质,其受体属于G蛋白偶联的7次跨膜受体超家族.越来越多的证据表明趋化因子与肿瘤生长、侵袭和转移密切相关.现综述趋化因子在肿瘤细胞增殖、迁移、粘附、降解细胞外基质、肿瘤血管生成及肿瘤器官特异性转移等过程中的作用.     

趋化因子CCL18与肿瘤

趋化因子CCL18通过招募炎症细胞参与机体的免疫和炎症过程,发挥免疫调控作用.在肿瘤患者血清及某些肿瘤组织中CCL18蛋白表达明显增加.然而CCL18在肿瘤中是发挥促癌作用还是抑癌作用尚存在争议.研究CCL18的作用及作用机制能够为肿瘤诊治提供新的靶向目标.     

趋化因子与肺癌

趋化因子与其相应的受体作用,广泛参与生物活动及病理过程。研究发现多种肿瘤细胞都过表达功能性的趋化因子。在肺癌中,趋化因子参与了其增殖、凋亡、侵袭和转移等过程。肺癌过表达的趋化因子及其受体,可作为明确的靶向目标进行针对性的抗肿瘤治疗。     

DLC-1基因在不同淋巴道转移潜能小鼠肝癌细胞系中表达的研究

目的:探讨DLC-1基因在小鼠肝癌淋巴道转移中的作用。方法:采用实时定量聚合酶链反应(RQ-PCR)方法检测DLC-1基因在淋巴道低转移潜能的小鼠肝癌细胞系Hca-P和高转移潜能的小鼠肝癌细胞系Hca-F中的表达水平。结果:Hca-P和Hca-F细胞系DLC-1基因表达分别为(3.83±0.45)×10-3和(2.02±0.13)×10-3,差异有统计学意义,P<0.01。随转移潜能的增高,DLC-1基因表达水平下降。免疫荧光细胞化学分析显示,DLC-1在低转移细胞株Hca-P中的荧光表达强度高于高转移细胞株Hca-F。结论:DLC-1基因作为转移抑制相关的基因,在肝癌的淋巴道侵袭转移中可能有着重要作用。DLC-1基因表达水平有可能成为预测肝癌转移的指标和基因治疗中新的靶点。     

人前列腺癌高低转移细胞株差异表达基因的筛选

目的：筛选高低转移能力人前列腺癌细胞株PC3M-1E8和PC3M-2B4间差异表达基因。方法：应用抑制性消减杂交（SSH）技术,对高转移能力人前列腺癌细胞株PC3M-1E8及其同源低转移细胞株PC3M-2B4进行2次消减杂交,第1次SSH实验,以PC3M-2B4细胞株为实验方,PC3M-1E8株为驱动方,构建正向消减文库。第2次实验则以PC3M-1E8株为实验方,PC3M-2B4为驱动方,构建反向消减文库。筛选出来的阳性克隆进行测序,并在GeneBank数据库中进行同源性比较后从中选取若干序列进行实时定量PCR验证。结果：2个消减文库共得到238个阳性克隆,从中各随机选取8个克隆测序并进行同源性分析,发现其中12条序列来自于11个已知基因,另外4条序列为新的未知功能的基因序列标签（EST）。结论：成功构建了高低转移力人前列腺癌细胞株的双向消减杂交文库。     

Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials.

Trans-resveratrol, a polyphenol present in red wines and various human foods, is an antioxidant also with reported chemopreventive properties. However, whether resveratrol may exert different effects in malignant cells with a common anatomical origin yet displaying different invasive characteristics is not known. Since invasiveness and metastasis are considered to be the most insidious and life-threatening aspects for all cancers, we compared the ability of resveratrol to control growth and cell cycle transition in the highly invasive MDA-MB-435 with the minimally invasive MCF-7 breast carcinoma cells. The data revealed that resveratrol exerted a greater inhibitory effect on the MDA-MB-435 cells. A diminution of percentage of cells in G1 phase and a corresponding accumulation of cells in S phase of the cell cycle was observed. We also studied the effect of resveratrol on a panel of MDA-MB-435 cells transfected with nm23-H1 and nm23-H2 genes, which have been suggested to play a role in controlling metastasis in breast cancer cells. These cells are designated as Vbeta, 1beta, 1Tbeta, 2beta, and 2Tbeta, respectively. The control Vbeta consists of MDA-MB-435 cells transfected with bacterial beta-glucuronidase. Cells labeled 1beta and 1Tbeta correspond to those carrying beta-glucuronidase and overexpressed wild-type (His118) or mutant (Tyr118, catalytically inactive) nm23-H1 genes. The 2beta and 2Tbeta refer to cells transfected with wild-type and mutant nm23-H2 genes. The responses of these cells to resveratrol were assessed by measuring proliferation, cell cycle phase distribution, and changes in expression of several genes. These studies have shown that resveratrol (25 microM, 3 days) reduced growth of all cell types by 60-80%. Overexpression of both wild-type and catalytically inactive nm23-H1 (1beta, 1Tbeta) but not nm23-H2 (2beta, 2Tbeta) reduced the proportion of cells in G1 phase, compared to the Vbeta control cells. Little changes in expression of PCNA, Rb, p53, and bcl-2 were observed in the five cell types treated with resveratrol, compared to untreated cells. Noted exceptions included reduced expression of Rb protein and increased expression of p53 in 2beta and 2Tbeta cells, and increased expression of bcl-2 in 2beta cells, treated with resveratrol. In contrast, resveratrol upregulated expression of cathepsin D by 50-100% in all cell lines except 1beta. These results suggest that the intrinsic metastatic potential of cancer cells may affect their responses to chemopreventive agents such as resveratrol.     

Androgen receptor gene expression in human prostate carcinoma cell lines

Responses to androgen vary widely among prostate cancers and prostatic carcinoma cell lines. We have explored the basis for this heterogeneity by examining the levels of androgen receptor expression in a prostate carcinoma cell line (LNCaP) that expresses the androgen receptor and two prostate carcinoma cell lines that do not contain detectable androgen receptor. We find that while the LNCaP cell line contains high levels of both the androgen receptor protein and mRNA, the receptor-negative cell lines DU-145 and PC-3 do not express androgen receptor protein as detected by immunoblotting or mRNA as detected by Northern analysis or S1 nuclease protection. These results indicate that the absence of androgen receptor expression in the androgen receptor-negative cell lines is caused by diminished androgen receptor mRNA levels. Genomic Southern analysis indicates that the differences in androgen receptor expression in each of these cell lines is not associated with detectable alterations in the structure of the androgen receptor gene.     

Global gene expression profiles of human head and neck squamous carcinoma cell lines

For genomewide monitoring and identification of biomarkers of head and neck squamous cell carcinoma (HNSCC), we have conducted a systematic characterization of gene expression profiles, using human cDNA microarrays containing 9K clones, in 25 HNSCC cell lines and 1 immortalized human oral keratinocyte cell line. We used normal human oral keratinocytes (NHOKs) as a reference. Our study showed that genes primarily involved in cell cycle regulation, oncogenesis, cell proliferation, differentiation, apoptosis and cell adhesion were widely altered in the 26 cell lines. Upregulated genes included known oncogenes, protein kinases, DNA-binding proteins and cell cycle regulators, while those commonly downregulated included differentiation markers, cell adhesion proteins, extracellular matrix proteins, structural proteins (keratins) and protease inhibitor proteins. Compared to NHOK, we observed a striking reduction in the expression of genes involved in terminal differentiation, suggesting that a loss in this process is an important signature of HNSCC. In addition, hierarchical clustering analysis as well as principal component analysis revealed 2 distinctive subtypes of gene expression patterns among the 26 cell lines, reflecting a degree of heterogeneity in HNSCC. By applying significance analysis of microarrays, 128 genes were selected for being distinctively expressed between the 2 groups. Genes differentially expressed in the 2 subgroups include cell proliferation-related genes, IGFBP6, EGFR and VEGFC; tumor suppression and apoptosis-related genes such as Tp53, Tp63; as well as cell cycle regulators such as CCND1 and CCND2 (cyclins D1 and D2), suggesting that the 2 subgroups might have undergone different pathways of carcinogenesis.     

COMPARATIVE ANALYSIS OF LYMPHATIC METASTASIS——ASSOCIATED GENES IN MOUSE HEPATOCELLULAR CARCINOMA CELL LINES WITH DIFFERENT METASTATIC POTENTIAL

Objective： To investigate the neoplasm lymphatic metastasis-associated genes and its molecular mechanisms. Methods： 22690 mouse genome cDNA microarrays （including 14500 known genes and 4371 ESTs） were used to compare and analyze the gene expression profiles of mouse hepatocellular carcinoma cell lines Hca-F （highly lymphatic metastasis potential） and Hca-P （low potential）. Results： 901 genes and 129 ESTs were up-regulated at least 2-fold in Hca-F cell. 33 genes showing significant alterations in expression were presented, including endoglin （EDG）, MCAM, Cdc42ep5, F2r, D7Ertd458e, Serpin hl （HSP47）, AXL, Areg and so on. These genes have functions of angiogenesis, cell adhesion, signal transduction, cell motility, chaperone activity, protein kinase activity and receptor binding. Conclusion： cDNA microarray combined with lymphatic metastasis models might contribute new methods and clues to the neoplasm lymphatic metastasis research. Some overexpressed genes might provide novel clues to the molecular mechanisms of neoplasm lymphatic metastasis.