SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers.
SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers.
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DOI：
10.1186/1471-2407-6-252
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发表时间：
2006-10-24
期刊：
影响因子：
3.8
通讯作者：
Whitehall VL
中科院分区：
文献类型：
--
作者：
Chia JA;Simms LA;Cozzi SJ;Young J;Jass JR;Walsh MD;Spring KJ;Leggett BA;Whitehall VL
SnoN是转化生长因子β（TGFβ）信号通路的重要调节因子，已显示出肿瘤促进和抑制活性。为了进一步探索这种复杂分子在结直肠肿瘤发生中的作用，我们检查了52对正常和肿瘤结直肠标本，按微卫星不稳定性水平分层; 18例高水平微卫星不稳定性（MSI-H）和34例微卫星稳定（MSS）。通过实时PCR定量SnoN转录表达，并分析预后的临床指标。在MSI-H亚组中，SnoN通常上调（6/18，33%）或下调（7/18，39%）。与MSI-H相比，在MSS癌中观察到显著不同的SnoN表达分布（P ≤ 0.001）。虽然17/34（50%）的MSS肿瘤表现出上调，没有显示出下调的表达。在MSI-H亚组中，上调与TGFβRII基因中缺乏重复序列突变显著相关（P ≤ 0.025），表明在存在功能性TGFβ信号传导的情况下，SnoN更频繁上调。这些数据共同支持SnoN具有致癌和肿瘤抑制特性的概念，这取决于肿瘤内的其他遗传变化，并且结直肠肿瘤发生的MSI-H途径为研究这些相反的功能提供了一个很好的模型。
SnoN is an important regulator of the transforming growth factor beta (TGFβ) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity. To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). SnoN transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis. Within the MSI-H subgroup, SnoN was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of SnoN expression was observed in MSS cancers compared with MSI-H (P ≤ 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the TGFβRII gene (P ≤ 0.025), suggesting that SnoN is more frequently up-regulated in the presence of functional TGFβ signalling. Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions.
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影响因子：
8
作者：
Cohen, SB;Nicol, R;Stavnezer, E
通讯作者：
Stavnezer, E
影响因子：
8
作者：
Takenoshita, S;Tani, M;Harris, CC
通讯作者：
Harris, CC
影响因子：
6.4
作者：
Chang, SC;Lin, JK;Chi, CW
通讯作者：
Chi, CW
影响因子：
11.4
作者：
Shinagawa, T;Dong, HD;Ishii, S
通讯作者：
Ishii, S
DOI：
10.1067/mlc.2002.120425
发表时间：
2002-01-01
期刊：
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子：
--
作者：
Ni, HM;Leong, AFPK;Hooi, SC
通讯作者：
Hooi, SC