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Steroid Receptor and Growth Factor Receptor Expression in Human Nonsmall Cell Lung Cancers Using Cells Procured by Laser-capture Microdissection

机译:使用激光捕获微散射采购的细胞,使用激光捕获微粉的细胞的类固醇受体和生长因子受体表达

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Few biomarkers exist for management of nonsmall cell lung cancers (NSCLC), although estrogen receptor (ERa and ERbeta) and EGF receptor (EGFR) expression has been related to clinical outcome (1-6). To circumvent problems of cellular heterogeneity in whole tissue, relative gene expression of ERa, ERbeta, EGFR, and HER-2 (c-erb-B2) was examined in pure lung carcinoma (LC) cells and normal epithelia by LCM. Cell-specific RNA was isolated and purified for RT-qPCR and microarray. Comparison of NSCLC cells to normal epithelia indicated increased levels of mRNA expression of ERbeta, ERa, EGFR, and HER-2 by 31%, 38%, 54%, and 62%, respectively, in LCs. The majority of NSCLC exhibiting low ERa and high HER-2 expression were from smokers. Although there was no correlation between ERbeta or EGFR expression and smoking history, there appeared to be an inverse relationship between levels of ERbeta and EGFR mRNAs in normal and neoplastic lung. Additionally, microarray analyses of LCM cells revealed >2,000 genes significantly altered in LC compared with normal epithelia. Herein, differences in NSCLC gene expression and normal lung cells were noted between specimens from gender and smoking groups. Microarray data revealed ERa expression was associated with alterations in <20 genes while ER3 expression revealed >500 associated genes, suggesting a more prominent role for ERbeta in lung. HER-2 mRNA levels appeared associated with > 1,000 genes, while EGFR mRNA levels were associated with far fewer genes. Collectively, results suggest quantitative genomic analyses of pure cell populations allow more accurate interpretation of LC status, which is being correlated with clinical outcome.
机译:少数生物标志物存在用于Nonsmall细胞肺癌(NSCLC)的管理,尽管雌激素受体(ERA和ERBETA)和EGF受体(EGFR)表达与临床结果有关(1-6)。为了在纯肺癌(LC)细胞(LCM的纯肺癌(LC)细胞中,通过LCM检查时代,ERBETA,EGFR和HER-2(C-ERB-B2)的相对基因表达,ERA,ERBETA,EGFR和HER-2(C-ERB-B2)中的相对基因表达。分离细胞特异性RNA并纯化用于RT-QPCR和微阵列。 NSCLC细胞对正常上皮细胞的比较表明,在LCs中,Erbeta,ERA,EGFR和HER-2的MRNA表达的水平分别增加了31%,38%,54%和62%。大多数NSCLC表现出低的时代和高海2表达都来自吸烟者。虽然Erbeta或EGFR的表达和吸烟历史之间没有相关性,但似乎是正常和肿瘤肺中erbeta和EGFR mRNA水平之间的反比关系。另外,LCM细胞的微阵列分析显示在LC中的> 2,000基因与正常上皮相比,LC显着改变。在此,在来自性别和吸烟组的标本之间注意到NSCLC基因表达和正常肺细胞的差异。微阵列数据显示ERA表达与<20个基因的改变相关,而ER3表达显示出> 500个相关基因,表明肺肉肉菌的作用更加突出。 HER-2 mRNA水平出现与> 1,000个基因相关,而EGFR mRNA水平与较少的基因相关。结果,结果表明纯细胞种群的定量基因组分析允许更准确地解释LC状态,与临床结果相关。

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