The role of COX-2 in breast and cervical cancer.
The role of COX-2 in breast and cervical cancer.
复制标题
COX-2 在乳腺癌和宫颈癌中的作用。
DOI：
10.1159/000071368
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Howe,LouiseR
中科院分区：
文献类型：
--
作者：
Dannenberg,AndrewJ;Howe,LouiseR
The inducible prostaglandin (PG) synthase COX-2 is strongly implicated in colorectal cancer by a wealth of evidence including epidemiological analyses and expression data. More recently, it has become apparent that COX-2 is also overexpressed in numerous other human malignancies and premalignant conditions, and may be a broadly relevant molecular target for chemopreventive and therapeutic intervention. Normally, cyclooxygenase-derived prostanoids contribute to many physiological processes including hemostasis, platelet aggregation, kidney and gastric function, reproduction, pain and fever. In particular, COX-2 is required for post-natal renal development and several female reproductive processes. Additionally, COX-2 is upregulated in response to growth factors, oncogenes and inflammatory stimuli, and thus contributes to increased PG synthesis in inflamed and neoplastic tissues. Cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and sulindac, which are commonly used to relieve pain and inflammation. Several epidemiological studies have reported inverse correlations between colon cancer incidence and NSAID use [1–5], suggesting that aberrant COX activity contributes to colorectal neoplasia. Consistent with this, NSAID administration reduces tumor incidence and multiplicity in rodent models of intestinal tumorigenesis, and selective COX-2 inhibitors are similarly effective in preventing intestinal tumors [6]. Two complementary genetic approaches have provided definitive evidence that COX-2 is important for tumorigenesis. Firstly, tumor formation in a mouse model of familial adenomatous polyposis is markedly reduced by genetic ablation of COX-2 [7]. Intestinal tumor incidence was reduced to 34% in COX-2 heterozygotes and to 14% in COX-2-null mice, relative to COX-2 wild-type
