Notch1 phenotype and clinical stage progression in non-small cell lung cancer.
Notch1 phenotype and clinical stage progression in non-small cell lung cancer.
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DOI：
10.1186/s13045-014-0104-2
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发表时间：
2015-02-06
影响因子：
28.5
通讯作者：
Yang SX
中科院分区：
文献类型：
--
作者：
Nguyen D;Rubinstein L;Takebe N;Miele L;Tomaszewski JE;Ivy P;Doroshow JH;Yang SX
NOTCH1跨膜受体通过配体结合触发的蛋白水解酶被激活，释放后，胞内结构域(N1-ICD)移位到细胞核内，调节靶基因的转录。Notch激活与包括非小细胞肺癌(NSCLC)在内的越来越多的人类恶性肿瘤的发生有关。然而，Notch1在NSCLC中的不同表达模式和激活状态与肿瘤进展的关系仍有待确定。应用免疫组织化学方法检测58例I~IV期非小细胞肺癌组织中NOTCH1和激活的Notch1、N1-ICD的表达。通过相关系数r统计分析Notch1或N1-ICD的表达与临床病理因素的相关性。P值是双面的。29例可检测到Notch1肿瘤，主要定位于细胞膜和细胞质(50%，95%Blyth-Stire-Casella可信区间37-63%)。与临床分期(r = -0.43，P <； 0.001)和淋巴结状态(r = -0.33，P = 0.01)呈负相关，与肿瘤大小无关。相反，核N1-ICD的表达水平很低，在12%的NSCLC患者中发现，与分期或淋巴结状态无关。在体外激活Notch1后，癌细胞中的核外染色基本上变成了核信号。大部分失活表型中的NOTCH1与非小细胞肺癌的临床分期呈负相关。NOTCH1，而不是激活的N1-ICD，可能是一个上下文依赖的淋巴结转移限制因子。
Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis.
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DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
影响因子：
3.3
作者：
Galluzzo P;Bocchetta M
通讯作者：
Bocchetta M
影响因子：
3.2
作者：
Wang Z;Li Y;Kong D;Sarkar FH
通讯作者：
Sarkar FH
影响因子：
10.5
作者：
Timmerman, LA;Grego-Bessa, J;de la Pompa, JL
通讯作者：
de la Pompa, JL
影响因子：
5.3
作者：
Rand, MD;Grimm, LM;Aster, JC
通讯作者：
Aster, JC