Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer.

Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer.
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诱导型微粒体前列腺素 E 合酶在结直肠腺瘤和癌症中过度表达。

DOI:
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发表时间:
2001
影响因子:
11.5
通讯作者:
A. Dannenberg
A. Dannenberg
中科院分区:
医学1区
文献类型:
--
作者:
K. Yoshimatsu;D. Golijanin;P. Paty;R. Soslow;Per;R. DeLellis;K. Subbaramaiah;A. Dannenberg

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最近发现了一种可诱导微粒体人前列腺素E合成酶(mPGES)。这种酶将环氧化酶(COX)产物前列腺素(PG) H(2)转化为PGE(2), PGE(2)是一种与致癌有关的类二十烷酸。在包括结直肠腺瘤和癌症在内的许多肿瘤类型中都观察到PGE(2)的增加。为了进一步阐明结肠直肠癌中PGE(2)水平升高的机制,我们测定了18对结直肠癌样本(肿瘤和邻近正常)中mPGES和COX-2的含量。通过免疫印迹分析,mPGES在83%的结直肠癌中过表达。COX-2在这些肿瘤中也普遍上调;在不同肿瘤中,mPGES和COX-2的上调程度存在显著差异。免疫组织化学显示,与邻近的正常结肠上皮细胞相比,结直肠腺瘤和癌的肿瘤细胞的mPGES免疫反应性增加。通过细胞培养研究mPGES和COX-2的调控作用。鹅去氧胆酸盐在结直肠癌细胞中显著诱导COX-2,但不诱导mPGES。肿瘤坏死因子α对mPGES和COX-2均有诱导作用,但诱导时间和诱导程度不同。正如之前关于COX-2的报道,过表达Ras导致mPGES启动子活性增加数倍。综上所述,我们的研究结果表明,在结直肠腺瘤和癌症中,mPGES和COX-2的过表达有助于增加PGE(2)的含量。控制这两种酶表达的机制并不相同。
Recently, an inducible microsomal human prostaglandin E synthase (mPGES) was identified. This enzyme converts the cyclooxygenase (COX) product prostaglandin (PG) H(2) to PGE(2), an eicosanoid that has been linked to carcinogenesis. Increased amounts of PGE(2) have been observed in many tumor types including colorectal adenomas and cancers. To further elucidate the mechanism responsible for increased levels of PGE(2) in colorectal tumors, we determined the amounts of mPGES and COX-2 in 18 paired samples (tumor and adjacent normal) of colorectal cancer. With immunoblot analysis, mPGES was overexpressed in 83% of colorectal cancers. COX-2 was also commonly up-regulated in these tumors; marked differences in the extent of up-regulation of mPGES and COX-2 were observed in individual tumors. Immunohistochemistry revealed increased mPGES immunoreactivity in neoplastic cells in both colorectal adenomas and cancers compared with adjacent normal colonic epithelium. Cell culture was used to investigate the regulation of mPGES and COX-2. Chenodeoxycholate markedly induced COX-2 but not mPGES in colorectal cancer cells. Tumor necrosis factor-alpha induced both mPGES and COX-2, but the time course and magnitude of induction differed. As reported previously for COX-2, overexpressing Ras caused a several-fold increase in mPGES promoter activity. Taken together, our results suggest that overexpression of mPGES in addition to COX-2 contributes to increased amounts of PGE(2) in colorectal adenomas and cancer. The mechanisms controlling the expression of these two enzymes are not identical.
DOI: --
发表时间: 1998-01
期刊: Cancer research
影响因子: 11.2
作者:
H. Sheng;J. Shao;J. Morrow;R. Beauchamp;R. Dubois
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DOI: --
发表时间: 1997
期刊: Cancer research.
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发表时间: 1998-03
期刊: Cancer research
影响因子: 11.2
作者:
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通讯作者: Min Huang;M. Stolina;Sherven P Sharma;J. Mao;Li Zhu;Patrice W. Miller;J. Wollman;H. Herschman;S. Dubinett
DOI: --
发表时间: 1999-04
期刊: Cancer research
影响因子: 11.2
作者:
L. R. Howe;L. R. Howe;K. Subbaramaiah;K. Subbaramaiah;W. Chung;W. Chung;Andrew J. Dannenberg;Anthony M. C. Brown;Anthony M. C. Brown
通讯作者: L. R. Howe;L. R. Howe;K. Subbaramaiah;K. Subbaramaiah;W. Chung;W. Chung;Andrew J. Dannenberg;Anthony M. C. Brown;Anthony M. C. Brown
人类子宫内膜腺癌中环氧合酶 2 和过氧化物酶体增殖物激活受体 δ 的表达升高。
DOI: 10.1038/sj.neo.7900119
发表时间: 2000
期刊: Neoplasia (New York, N.Y.)
影响因子: --
作者:
Tong,BJ;Tan,J;Tajeda,L;Das,SK;Chapman,JA;DuBois,RN;Dey,SK
通讯作者: Dey,SK