Induction of retinoic acid receptor-β suppresses cyclooxygenase-2 expression in esophageal cancer cells
Induction of retinoic acid receptor-β suppresses cyclooxygenase-2 expression in esophageal cancer cells
复制标题
DOI：
10.1038/sj.onc.1205106
复制
发表时间：
2002-01-17
期刊：
影响因子：
8
通讯作者：
Xu, XC
中科院分区：
文献类型：
--
作者：
Li, M;Song, SM;Xu, XC
由于视黄酸受体（RAR）-β mRNA在食管癌发生过程中经常丢失，并且不表达RAR-β的食管癌细胞对视黄酸（RA）具有抗性，我们将RAR-β表达载体稳定转染到食管癌细胞系TE-8中，并将反义RAR-β转染到TE-3细胞中。RAR-β转染降低TE-8细胞的细胞生长和集落形成，并诱导细胞凋亡。反义RAR-β转染的TE-3细胞具有较短的倍增时间，并对RA产生抗性。RAR-β的诱导降低了RAR-β转染的TE-8细胞中考克斯-2的表达，而反义RAR-β转染的TE-3细胞增加了考克斯-2的表达。RAR-β对考克斯-2表达的抑制作用在RA存在下进一步增强，其被RAR拮抗剂阻断。不能有效结合RAR-β的合成类维生素A N-（4-羟基苯基）-视黄酰胺对考克斯-2抑制没有影响。此外，RA仅在RAR-β阳性细胞中阻断胆汁酸诱导的考克斯-2表达和前列腺素E-2产生。我们的数据表明，RAR-β的抗癌作用可能与其抑制考克斯-2表达的能力有关，并支持RAR-β表达的缺失可能有助于食管癌的发生。
Since retinoic acid receptor (RAR)-beta mRNA is frequently lost during esophageal carcinogenesis and esophageal cancer cells that do not express RAR-beta are resistant to retinoic acid (RA), we stably transfected RAR-beta expression vector into an esophageal cancer cell line TE-8 and an antisense RAR-beta into TE-3 cells. Transfection of RAR-beta decreased cell growth and colony formation and induced apoptosis in TE-8 cells. Antisense RAR-beta-transfected TE-3 cells had a shorter doubling time and became resistant to RA. Induction of RAR-beta decreased COX-2 expression in RAR-beta transfected TE-8 cells, whereas antisense RAR-beta transfected TE-3 cells increased COX-2 expression. The inhibitory effect of RAR-beta on COX-2 expression was further enhanced in the presence of RA, which was blocked by an RAR antagonist. The synthetic retinoid N-(4-hydroxyphenyl)-retinamide, which does not bind effectively to RAR-beta, had no effect on COX-2 suppression. Furthermore, RA blocked bile acid-induced COX-2 expression and prostaglandin E-2 production only in the RAR-beta positive cells. Our data demonstrated that anticancer effect of RAR-beta may be related to its ability to suppress COX-2 expression and support that the loss of RAR-beta expression may contribute to esophageal carcinogenesis.