Tong B J, Tan J, Tajeda L, Das S K, Chapman J A, DuBois R N, Dey S K
Department of Obstetrics and Gynecology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Neoplasia. 2000 Nov-Dec;2(6):483-90. doi: 10.1038/sj.neo.7900119.
Epidemiological studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduce the risk and mortality from colorectal cancer, in part by inhibiting prostaglandin (PG) synthesis. Cyclooxygenase (COX), the rate-limiting enzyme in PG biosynthesis, exists in two isoforms, COX-1 and COX-2. Genetic and pharmacological evidence suggest that COX-2 is involved in the development of colorectal cancer. We have previously shown that COX-2-derived prostacyclin participates in blastocyst implantation through activation of peroxisome proliferator activated receptor delta (PPARdelta), a member of the nuclear hormone receptor family. Furthermore, our recent studies suggest that a similar pathway is operative during colorectal carcinogenesis. These observations prompted us to examine whether the COX-2-PPARdelta signaling pathway is also involved during development of uterine adenocarcinoma. Here we describe for the first time the heightened expression of COX-2 and PPARdelta, but not COX-1, in uterine endometrial adenocarcinoma.
流行病学研究表明，非甾体抗炎药（NSAIDs）可显著降低结直肠癌的风险和死亡率，部分原因是其抑制了前列腺素（PG）的合成。环氧化酶（COX）是PG生物合成中的限速酶，有两种同工型，即COX-1和COX-2。遗传学和药理学证据表明，COX-2与结直肠癌的发生有关。我们之前已表明，COX-2衍生的前列环素通过激活核激素受体家族成员过氧化物酶体增殖物激活受体δ（PPARδ）参与胚泡着床。此外，我们最近的研究表明，类似的途径在结直肠癌发生过程中也起作用。这些观察结果促使我们研究COX-2-PPARδ信号通路是否也参与子宫内膜腺癌的发生。在此，我们首次描述了COX-2和PPARδ而非COX-1在子宫内膜腺癌中表达上调。
