Genetic deletion of microsomal prostaglandin E synthase-1 suppresses mouse mammary tumor growth and angiogenesis.
Genetic deletion of microsomal prostaglandin E synthase-1 suppresses mouse mammary tumor growth and angiogenesis.
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DOI：
10.1016/j.prostaglandins.2013.04.002
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发表时间：
2013-10
影响因子：
2.9
通讯作者：
Dannenberg AJ
中科院分区：
文献类型：
--
作者：
Howe LR;Subbaramaiah K;Kent CV;Zhou XK;Chang SH;Hla T;Jakobsson PJ;Hudis CA;Dannenberg AJ
环氧合酶/前列腺素（考克斯/PG）信号通路在炎症和肿瘤形成中具有核心重要性。考克斯抑制剂广泛用于镇痛，并且还显示出对癌症预防的活性。然而，与这类药物相关的心血管毒性降低了它们的临床效用，并促使开发更安全的方法来缓解疼痛和预防癌症。微粒体前列腺素E合成酶1（mPGES-1）作为一个潜在的靶点引起了人们的广泛关注。在结直肠癌和乳腺癌中均观察到mPGES-1的过表达，基因敲除和过表达方法已确定mPGES-1在胃肠道癌发生中的作用。在这里，我们使用基因敲除方法评估mPGES-1对乳腺肿瘤发生的贡献。将mPGES-1缺陷的小鼠与乳腺癌由人表皮生长因子受体2（HER 2/neu）过表达驱动的品系杂交。mPGES-1的缺失与HER 2/neu转基因小鼠乳腺内PGE 2水平、芳香化酶活性和乳腺血管生成的显著降低相关。与这些发现一致，我们观察到直径≥ 1 mm的肿瘤的多样性显著降低，表明mPGES-1有助于乳腺肿瘤生长。我们的数据将mPGES-1确定为潜在的抗乳腺癌靶点。
The cyclooxygenase/prostaglandin (COX/PG) signaling pathway is of central importance in inflammation and neoplasia. COX inhibitors are widely used for analgesia and also have demonstrated activity for cancer prophylaxis. However, cardiovascular toxicity associated with this drug class diminishes their clinical utility and motivates the development of safer approaches both for pain relief and cancer prevention. The terminal synthase microsomal PGE synthase-1 (mPGES-1) has attracted considerable attention as a potential target. Overexpression of mPGES-1 has been observed in both colorectal and breast cancers, and gene knockout and overexpression approaches have established a role for mPGES-1 in gastrointestinal carcinogenesis. Here we evaluate the contribution of mPGES-1 to mammary tumorigenesis using a gene knockout approach. Mice deficient in mPGES-1 were crossed with a strain in which breast cancer is driven by overexpression of human epidermal growth factor receptor 2 (HER2/neu). Loss of mPGES-1 was associated with a substantial reduction in intramammary PGE2 levels, aromatase activity, and angiogenesis in mammary glands from HER2/neu transgenic mice. Consistent with these findings, we observed a significant reduction in multiplicity of tumors ≥1mm in diameter, suggesting that mPGES-1 contributes to mammary tumor growth. Our data identify mPGES-1 as a potential anti-breast cancer target.
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影响因子：
3.9
作者：
Chen, S;Zhou, D;Yang, C
通讯作者：
Yang, C
DOI：
10.1186/bcr1678
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Howe LR
通讯作者：
Howe LR
影响因子：
158.5
作者：
Bertagnolli, Monica M.;Eagle, Craig J.;Hawk, Ernest T.
通讯作者：
Hawk, Ernest T.
影响因子：
3.7
作者：
Finetti F;Terzuoli E;Bocci E;Coletta I;Polenzani L;Mangano G;Alisi MA;Cazzolla N;Giachetti A;Ziche M;Donnini S
通讯作者：
Donnini S
影响因子：
5.8
作者：
Bruno, Annalisa;Di Francesco, Luigia;Patrignani, Paola
通讯作者：
Patrignani, Paola