Prevention of tumorigenesis in p53-null mammary epithelium by rexinoid bexarotene, tyrosine kinase inhibitor gefitinib, and celecoxib.
Prevention of tumorigenesis in p53-null mammary epithelium by rexinoid bexarotene, tyrosine kinase inhibitor gefitinib, and celecoxib.
复制标题
DOI：
10.1158/1940-6207.capr-08-0107
复制
发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Brown PH
中科院分区：
文献类型：
--
作者：
Medina D;Kittrell F;Hill J;Zhang Y;Hilsenbeck SG;Bissonette R;Brown PH
The chemopreventive effects of three agents, rexinoid bexarotene, tyrosine kinase inhibitor gefitinib and celecoxib, were tested on mammary tumor development arising in p53 null mammary epithelium. The rexinoid bexarotene was the most efficacious inhibitor as it reduced mammary tumor development by 75% in virgin mice and significantly delayed mean tumor development by 98 days in hormone stimulated mice. The tyrosine kinase inhibitor gefitinib reduced mammary tumor incidence by 50% in virgin mice but did not significantly delay mean tumor latency in hormone stimulated mice. Celecoxib did not reduce tumor incidence or mean tumor latency in either of the two models. The high doses of the rexinoid and the tyrosine kinase inhibitor did not affect the progression of tumors arising from the premalignant mammary outgrowth line, PN8a. A comparison of these agents with tamoxifen shows the superiority of tamoxifen in preventing tumor development in p53 null mammary cells. Similarly, a comparison of the results of the p53 model with other transgenic models to the chemopreventive agents demonstrated that mammary tumors arising from different oncogenic events will respond differently to the different agents.
