Role of p53 in the progression of gastric cancer.
Role of p53 in the progression of gastric cancer.
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DOI：
10.18632/oncotarget.2434
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发表时间：
2014-12-15
期刊：
影响因子：
--
通讯作者：
Boussioutas A
中科院分区：
文献类型：
--
作者：
Busuttil RA;Zapparoli GV;Haupt S;Fennell C;Wong SQ;Pang JM;Takeno EA;Mitchell C;Di Costanzo N;Fox S;Haupt Y;Dobrovic A;Boussioutas A
肠化生(IM)是一种与胃癌(GC)相关的癌前病变，但在分子变化方面的描述很少。在这里，我们探讨了在胃癌中常见的突变基因TP53的作用，以确定是否可以将p53蛋白表达和/或TP53体细胞突变的存在作为患者从IM进展到GC的风险的预测标志。采用免疫组织化学和高分辨熔融法分别检测正常胃粘膜、无并发GC的IM(IM-GC)、IM合并GC(IM+GC)和GC中的p53蛋白表达和TP53基因突变情况。这项比较研究显示，从正常粘膜到GC，随着疾病的进展，P53的表达水平逐渐增加。然而，在IM中未检测到TP53突变，而在GC中频繁发生突变。此外，我们还发现，在100%的IM+GC队列中，MDM2/x的蛋白表达增加，这些样本也显示出高水平的野生型p53蛋白。我们的数据表明，TP53突变发生在胃癌发生的晚期，有助于最终转化为癌症。我们还展示了MDMX在GC中的参与。
Intestinal metaplasia (IM) is a premalignant lesion associated with gastric cancer (GC) but is poorly described in terms of molecular changes. Here, we explored the role of TP53, a commonly mutated gene in GC, to determine if p53 protein expression and/or the presence of somatic mutations in TP53 can be used as a predictive marker for patients at risk of progressing to GC from IM. Immunohistochemistry and high resolution melting were used to determine p53 protein expression and TP53 mutation status respectively in normal gastric mucosa, IM without concurrent GC (IM-GC), IM with concurrent GC (IM+GC) and GC. This comparative study revealed an incremental increase in p53 expression levels with progression of disease from normal mucosa, via an IM intermediate to GC. TP53 mutations however, were not detected in IM but occurred frequently in GC. Further, we identified increased protein expression of Mdm2/x, both powerful regulators of p53, in 100% of the IM+GC cohort with these samples also exhibiting high levels of wild-type p53 protein. Our data suggests that TP53 mutations occur late in gastric carcinogenesis contributing to the final transition to cancer. We also demonstrated involvement of Mdmx in GC.
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影响因子：
7.3
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
通讯作者：
Brenton, James D.
影响因子：
24.5
作者：
FILIPE, MI;POTET, F;ZEEGEN, R
通讯作者：
ZEEGEN, R
影响因子：
6.4
作者：
Gonzalez, Carlos A.;Sanz-Anquela, Jose M.;Gisbert, Javier P.;Correa, Pelayo
通讯作者：
Correa, Pelayo
影响因子：
5.3
作者：
Lukashchuk, Natalia;Vousden, Karen H.
通讯作者：
Vousden, Karen H.
影响因子：
64.8
作者：
Laurie, Nikia A.;Donovan, Stacy L.;Dyer, Michael A.
通讯作者：
Dyer, Michael A.