Molecular characterizations of Nop16 in murine mammary tumors with varying levels of c-Myc.
Molecular characterizations of Nop16 in murine mammary tumors with varying levels of c-Myc.
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DOI：
10.1007/s11248-011-9529-3
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发表时间：
2012-04
影响因子：
3
通讯作者：
Rose-Hellekant TA
中科院分区：
文献类型：
--
作者：
Kundel DW;Stromquist E;Greene AL;Zhdankin O;Regal RR;Rose-Hellekant TA
NOP 16，也称为HSPC 111，已在体外研究中被鉴定为MYC和雌激素调节的基因，因此共表达水平强烈相关。重要的是，NOP 16的高表达与乳腺癌患者的不良临床结局相关。然而，NOP 16，MYC和雌激素受体（ESR 1）的共表达在肿瘤和细胞系中变化很大，表明转录调控根据病理环境而不同。本研究的目的是确定Nop 16，Myc和Esr 1在具有不同组织病理学和分子特征的小鼠乳腺肿瘤中的表达模式。我们假设具有相对高Myc水平的肿瘤环境与具有相对低Myc水平的肿瘤环境具有不同的共表达模式。我们测量了来自WAP-c-myc小鼠的高级别和频繁转移的肿瘤中Myc和Nop 16 mRNA和蛋白的水平。相比之下，Myc和Nop 16 mRNA和蛋白质水平在NRL-TGF α小鼠中发展的侵袭性较低的肿瘤中显著较低。来自两种小鼠系的肿瘤表达ESR 1蛋白，并且我们发现在两种模型中ESR 1 mRNA水平与Myc水平呈正相关。然而，Myc和Nop 16转录水平仅在来自NRL-TGFα小鼠的肿瘤中呈正相关。我们在正常乳腺导管和小叶的管腔细胞以及从NRL-TGF α小鼠获得的增生和肿瘤中，在细胞核中发现了显著的NOP 16蛋白，在细胞质中发现了不太显著的染色。这种染色模式在来自WAP-c-Myc小鼠的肿瘤中逆转，因为核染色微弱或不存在，而胞质染色更明显。总之，NOP 16的表达和定位的调节在具有高与低MYC水平的肿瘤环境中变化，并且证明了基于MYC水平对临床乳腺癌进行分层的重要性。
NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated gene in in vitro studies, hence coexpression levels were strongly correlated. Importantly, high expression of NOP16 was associated with poor clinical outcome in breast cancer patients. However, coexpression of NOP16, MYC and estrogen receptor (ESR1) varied widely in tumors and cell lines suggesting that transcriptional regulation differed according to pathological environments. The goal of this study was to determine the expression patterns of Nop16, Myc and Esr1 in murine mammary tumors with disparate histopathological and molecular features. We hypothesized that tumor environments with relatively high Myc levels would have different coexpression patterns than tumor environments with relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein in tumors from WAP-c-myc mice that were of high grade and metastasized frequently. In contrast, Myc and Nop16 mRNA and proteins levels were significantly lower in the less aggressive tumors that developed in NRL-TGFα mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1 mRNA levels correlated positively with Myc levels in both models. However, Myc and Nop16 transcript levels correlated positively only in tumors from NRL-TGFα mice. We identified prominent NOP16 protein in nuclei and less prominent staining in the cytoplasm of luminal cells of ducts and lobules from normal mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFα mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear staining was faint or absent and cytoplasmic staining more pronounced. In summary, the regulation of expression and localization of NOP16 varies in tumor environments with high versus low MYC levels and demonstrate the importance of stratifying clinical breast cancers based on MYC levels.
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影响因子：
12.3
作者：
Lin CY;Ström A;Vega VB;Kong SL;Yeo AL;Thomsen JS;Chan WC;Doray B;Bangarusamy DK;Ramasamy A;Vergara LA;Tang S;Chong A;Bajic VB;Miller LD;Gustafsson JA;Liu ET
通讯作者：
Liu ET
影响因子：
2.7
作者：
Nygaard S;Jacobsen A;Lindow M;Eriksen J;Balslev E;Flyger H;Tolstrup N;Møller S;Krogh A;Litman T
通讯作者：
Litman T
NOPdb：核仁蛋白质组数据库。
影响因子：
14.9
作者：
Leung AK;Trinkle-Mulcahy L;Lam YW;Andersen JS;Mann M;Lamond AI
通讯作者：
Lamond AI
影响因子：
2.8
作者：
Chen D;Dou QP
通讯作者：
Dou QP
影响因子：
7
作者：
Morin, Ryan D.;O'Connor, Michael D.;Marra, Marco A.
通讯作者：
Marra, Marco A.