Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer.
Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer.
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DOI：
10.1186/bcr3185
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发表时间：
2012-05-11
期刊：
影响因子：
--
通讯作者：
Hendrix MJ
中科院分区：
文献类型：
--
作者：
Strizzi L;Hardy KM;Margaryan NV;Hillman DW;Seftor EA;Chen B;Geiger XJ;Thompson EA;Lingle WL;Andorfer CA;Perez EA;Hendrix MJ
最近有报道称，在几种不同的人类癌症中，肿瘤生长因子-β(TGF-β)相关的胚胎形态原结节重新出现。在这项研究中，我们检测了一系列人乳腺良恶性组织中Nodal的表达，以确定该表达的临床意义以及Nodal是否可以作为乳腺癌的潜在治疗靶点。应用免疫组织化学方法对431例诊断为乳腺良恶性疾病的初诊患者的组织切片进行Nodal免疫组织化学染色和盲法分析。结节染色的程度随后与现有的临床数据相关，如诊断和疾病分期。在用结节阻断抗体处理的乳腺癌细胞系MDA-MB-231和MDA-MB-468中，进一步探索了这些组织发现，以确定靶点验证的生物学效应。所有样本均检测到不同程度的结节染色。未分化、晚期、浸润性乳腺癌的Nodal染色强度明显高于乳腺良性病变或早期乳腺癌。结节封闭抗体处理体外培养的人乳腺癌细胞后，细胞在软琼脂中的增殖和集落形成能力显著降低，同时细胞凋亡率增加。这些数据表明，Nodal作为疾病进展的生物标志物和乳腺癌抗Nodal治疗的有希望的靶点，具有潜在的作用。
The re-emergence of the tumour growth factor-beta (TGF-beta)-related embryonic morphogen Nodal has recently been reported in several different human cancers. In this study, we examined the expression of Nodal in a series of benign and malignant human breast tissues to determine the clinical significance of this expression and whether Nodal could represent a potential therapeutic target in breast cancer. Tissue sections from 431 therapeutically naive patients diagnosed with benign or malignant breast disease were stained for Nodal by immunohistochemistry and analysed in a blinded manner. The degree of Nodal staining was subsequently correlated with available clinical data, such as diagnoses and disease stage. These tissue findings were further explored in breast cancer cell lines MDA-MB-231 and MDA-MB-468 treated with a Nodal blocking antibody to determine biological effects for target validation. A variable degree of Nodal staining was detected in all samples. The intensity of Nodal staining was significantly greater in undifferentiated, advanced stage, invasive breast cancer compared with benign breast disease or early stage breast cancer. Treatment of human breast cancer cells in vitro with Nodal blocking antibody significantly reduced proliferation and colony-forming ability in soft agar, concomitant with increased apoptosis. These data suggest a potential role for Nodal as a biomarker for disease progression and a promising target for anti-Nodal therapy in breast cancer.
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影响因子：
45.3
作者：
Liu, Suling;Wicha, Max S.
通讯作者：
Wicha, Max S.
基于微阵列的乳腺癌分子分类的类别发现：观察者间一致性分析。
DOI：
10.1093/jnci/djr071
发表时间：
2011-04-20
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Mackay A;Weigelt B;Grigoriadis A;Kreike B;Natrajan R;A'Hern R;Tan DS;Dowsett M;Ashworth A;Reis-Filho JS
通讯作者：
Reis-Filho JS
影响因子：
11.8
作者：
Ben-Haim, Nadav;Lu, Cindy;Constam, Daniel B.
通讯作者：
Constam, Daniel B.
影响因子：
28.5
作者：
Santana-Davila R;Perez EA
通讯作者：
Perez EA
影响因子：
4.4
作者：
Papageorgiou, Irene;Nicholls, Peter K.;Harrison, Craig A.
通讯作者：
Harrison, Craig A.