Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer.
Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer.
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DOI：
10.1016/j.jamcollsurg.2009.12.008
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发表时间：
2010-05
影响因子：
5.2
通讯作者：
Evers, B. Mark
中科院分区：
文献类型：
--
作者：
Johnson, Sara M.;Gulhati, Pat;Rampy, Bill A.;Han, Yimei;Rychahou, Piotr G.;Doan, Hung Q.;Weiss, Heidi L.;Evers, B. Mark
PI 3 K/Akt/mTOR通路在结直肠癌（CRC）的生长和进展中起关键作用。我们的研究有两个目的：1）确定该途径的几个关键组分（包括p85α、Akt 1、Akt 2、p-mTORSer 2448和p-p70 S6 KThr 389）在CRC中的表达水平，2）将这些蛋白质的表达与癌症分期和位置（左侧与右侧）相关联。对154例患者的正常结肠和CRC进行p85α、Akt 1、Akt 2、p-mTORSer 2448和p-p70 S6 KThr 389的免疫组化。与来自同一患者的匹配的正常结肠组织相比，研究的所有蛋白质在CRC中显著过表达（p<0.0001）。PI 3 K通路组分蛋白在正常和恶性结肠组织中中度相关;与癌症中相同的相关性相比，正常组织中的相关性往往更强。p85α在IV期癌症中的表达水平显著高于I-III期癌症（p = 0.0005）;有趣的是，与早期阶段相比，IV期CRC患者的邻近正常结肠粘膜中的p85α表达也显著增加（p=0.003）。最后，左侧CRC中Akt 1、Akt 2和p-p70 S6 KThr 389的表达高于右侧CRC（分别为p = 0.007、p = 0.0008和p = 0.04）。PI 3 K/Akt/mTOR通路组分p85α、Akt 1、Akt 2、p-mTORSer 2448和p-p70 S6 KThr 389在CRC中高度过表达，因此为在CRC患者中治疗靶向该通路提供了理论基础。IV期患者邻近正常粘膜中p85α表达的增加提示重要的视野缺损，这可能有助于这些癌症的生长和进展。
The PI3K/Akt/mTOR pathway plays a critical role in the growth and progression of colorectal cancer (CRC). The purpose of our study was twofold: 1) to determine the expression levels of several key components of this pathway including p85α, Akt1, Akt2, p-mTORSer2448 and p-p70S6KThr389 in CRCs, and 2) to correlate the expression of these proteins with cancer stage and location (left- vs. right-sided). Immunohistochemistry for p85α, Akt1, Akt2, p-mTORSer2448 and p-p70S6KThr389 was performed on normal colon and CRCs from 154 patients. All proteins investigated were significantly overexpressed in CRCs compared to matched normal colonic tissue from the same patient (p<0.0001). The PI3K pathway component proteins were moderately correlated across normal and malignant colon tissues; correlations tended to be stronger in normal tissues as compared to the same correlations in cancers. Expression levels of p85α were significantly higher in Stage IV cancers than in Stage I–III cancers (p = 0.0005); interestingly, p85α expression was also significantly increased in the adjacent normal colonic mucosa of patients with Stage IV CRC compared with earlier stages (p=0.003). Finally, expression of Akt1, Akt2, and p-p70S6KThr389 was higher in left-sided CRCs compared with CRCs in the right colon (p = 0.007, p = 0.0008, and p = 0.04, respectively). The PI3K/Akt/mTOR pathway components, p85α, Akt1, Akt2, p-mTORSer2448 and p-p70S6KThr389, are highly overexpressed in CRCs thus providing the rationale for targeting this pathway therapeutically in CRC patients. The increased expression of p85α in the adjacent normal mucosa of Stage IV patients suggests an important field defect, which may contribute to the growth and progression of these cancers.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
DOI：
10.1158/1078-0432.ccr-09-1249
发表时间：
2009-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gulhati P;Cai Q;Li J;Liu J;Rychahou PG;Qiu S;Lee EY;Silva SR;Bowen KA;Gao T;Evers BM
通讯作者：
Evers BM
影响因子：
3.8
作者：
Rychahou, PG;Murillo, CA;Evers, BM
通讯作者：
Evers, BM
DOI：
10.1083/jcb.200408161
发表时间：
2004-11-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Manning BD
通讯作者：
Manning BD
影响因子：
50.3
作者：
Lim, KH;Counter, CM
通讯作者：
Counter, CM