Cheng R Y S, Birely L A, Lum N L, Perella C M, Cherry J M, Bhat N K, Kasprzak K S, Powell D A, Alvord W G, Anderson L M
Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Building 538, Ft Detrick, Frederick, Maryland 21701, USA.
J Mol Endocrinol. 2004 Feb;32(1):257-78. doi: 10.1677/jme.0.0320257.
Microarray technology was evaluated for usefulness in assessing relationships between serum corticosterone and hepatic gene expression. Nine pairs of female Swiss mice were chosen to provide a wide range of serum corticosterone ratios; cDNA microarray analysis (approximately 8000 genes) was performed on their livers. A statistical method based on calculation of 99% confidence intervals discovered 32 genes which varied significantly among the livers. Five of these ratios correlated significantly with serum corticosterone ratio, including tyrosine aminotransferase, stress-induced protein, pleiotropic regulator 1 and insulin-like growth factor-binding protein-1; the latter has a potential role in cancer development. Secondly, linear regression of gene expression vs corticosterone ratios was screened for those with r> or =0.8 (P<0.01), yielding 141 genes, including some known to be corticosterone regulated and others of interest as possible glucocorticoid targets. Half of these significant correlations involved data sets where no microarray ratio exceeded +/- 1.5. These results showed that microarray may be used to survey tissues for changes in gene expression related to serum hormones, and that even small changes in expression can be of statistical significance in a study with adequate numbers of replicate samples.
评估了微阵列技术在评估血清皮质酮与肝脏基因表达之间关系方面的实用性。选择了9对雌性瑞士小鼠以提供广泛的血清皮质酮比率范围;对它们的肝脏进行了cDNA微阵列分析(约8000个基因)。一种基于计算99%置信区间的统计方法发现了32个在肝脏之间有显著差异的基因。其中5个比率与血清皮质酮比率显著相关,包括酪氨酸转氨酶、应激诱导蛋白、多效调节因子1和胰岛素样生长因子结合蛋白-1;后者在癌症发展中具有潜在作用。其次,筛选基因表达与皮质酮比率的线性回归中r≥0.8(P<0.01)的情况,得到141个基因,其中包括一些已知受皮质酮调节的基因以及其他可能作为糖皮质激素靶标的感兴趣基因。这些显著相关性中有一半涉及微阵列比率未超过±1.5的数据集。这些结果表明,微阵列可用于检测组织中与血清激素相关的基因表达变化,并且在具有足够数量重复样本的研究中,即使是表达的微小变化也可能具有统计学意义。