Correlation of insulin-like growth factor-binding protein-3 messenger RNA with protein expression in primary breast cancer tissues: Detection of higher levels in tumors with poor prognostic features
Correlation of insulin-like growth factor-binding protein-3 messenger RNA with protein expression in primary breast cancer tissues: Detection of higher levels in tumors with poor prognostic features
复制标题
DOI：
10.1093/jnci/88.9.601
复制
发表时间：
1996-05-01
期刊：
影响因子：
--
通讯作者：
Yee, D
中科院分区：
文献类型：
--
作者：
Rocha, RL;Hilsenbeck, SG;Yee, D
背景资料：胰岛素样生长因子（IGF）结合蛋白（IGFBPs）通过影响IGF与IGF受体之间的相互作用来调节IGF的作用。IGFBP-3是六种已知IGFBP之一，是血清中主要的IGFBP，并由乳腺癌细胞表达。与雌激素受体（ER）阳性样品相比，ER阴性乳腺癌细胞系和肿瘤表达更高水平的IGFBP-3。因此，IGFBP-3的表达可能与乳腺癌生物学相关，尽管目前尚不清楚IGFBP-3水平是否与ER状态以外的其他乳腺癌预后因素相关。也不知道用于测量乳腺癌中IGFBP-3的不同方法如何相互关联。目的：我们通过不同方法测量乳腺肿瘤中IGFBP-3信使RNA（mRNA）和蛋白水平，以测试这些方法的比较情况，并研究IGFBP-3与乳腺癌预后因素之间的关系。研究方法：我们分析了40例人乳腺肿瘤，并通过配体印迹分析，免疫印迹分析，免疫放射分析（IRMA）和核糖核酸酶保护试验检测IGFBP-3的表达。另一组40例乳腺肿瘤，根据ER和孕激素受体（PR）的状态，S期，和倍性选择，通过IRMA分析。结果如下：在40个可以分离RNA的样本中，有26个（65%）IGFBP-3 mRNA水平与IRMA测量的IGFBP-3水平相关（双侧; P =.0001），但与配体印迹或免疫印迹测量的IGFBP-3水平无关。所有蛋白质测定中蛋白质水平高度相关。由于IRMA比配体印迹和免疫印迹分析更敏感和准确，我们使用IRMA检测另外20个具有不良预后特征（ER和PR阴性，高S期和非整倍体）的原发性乳腺肿瘤和20个具有良好预后因素（相反特征）的肿瘤中的IGFBP-3水平。IGFBP-3水平在具有不良预后特征的肿瘤中高3倍（平均值+/-标准差= 32.8 +/- 25.2 vs 11.8 +/- 9.7 ng/mg;双侧; P = 0.003）。结论：这些发现表明，在人乳腺癌中，IGFBP-3 mRNA和蛋白水平是相关的，并且在具有不良预后特征的肿瘤中可检测到较高水平的IGFBP-3。结论：IGFBP-3可能参与乳腺癌细胞生长的调控。
Background: The insulin-like growth factor (IGF)-binding proteins (IGFBPs) regulate the actions of the IGFs by influencing interactions between the IGFs and the IGF receptors. IGFBP-3, one of the six known species of IGFBPs, is the predominant IGFBP in serum and is expressed by breast cancer cells. Compared with estrogen receptor (ER)-positive samples, ER-negative breast cancer cell lines and tumors express higher levels of IGFBP-3. Therefore, expression of IGFBP-3 may be relevant in breast cancer biology, although it is unknown whether IGFBP-3 levels correlate with other breast cancer prognostic factors besides ER status. It is also not known how different methods used to measure IGFBP-3 in breast cancer correlate. Purpose: We measured IGFBP-3 messenger RNA (mRNA) and protein levels in breast tumors by different methods to test how these methods compare and to investigate the relationship between IGFBP-3 and breast cancer prognostic factors. Methods: We analyzed 40 human breast tumors and examined IGFBP-3 expression by ligand blot analysis, immunoblot analysis, immunoradiometric assay (IRMA), and ribonuclease protection assay. Another set of 40 breast tumors, selected according to ER and progesterone receptor (PR) status, S phase, and ploidy, was analyzed by IRMA. Results: In 26 (65%) of 40 samples in which RNA could be isolated, IGFBP-3 mRNA levels correlated with IGFBP-3 levels measured by IRMA (two-sided; P =.0001) but not with IGFBP-3 levels measured by ligand blot or immunoblot. Protein levels were highly correlated among all protein assays. Because the IRMA was more sensitive and accurate than the ligand blot and immunoblot assays, we used IRMA to examine IGFBP-3 levels in an additional 20 primary breast tumors with poor prognostic features (ER and PR negativity, high S phase, and aneuploidy) and in 20 tumors with good prognostic factors (opposite features). IGFBP-3 levels were threefold higher in tumors with poor prognostic features (mean +/- standard deviation = 32.8 +/- 25.2 versus 11.8 +/- 9.7 ng/mg; two-sided; P =.003). Conclusions: These findings suggest that in human breast cancer, IGFBP-3 mRNA and protein levels are correlated and higher levels of IGFBP-3 are detectable in tumors with poor prognostic features. Implications: IGFBP-3 may be involved in the regulation of breast cancer cell growth.