Cancer Prevention Research 2, 168, February 1, 2009. Published Online First January 27, 2009;
doi: 10.1158/1940-6207.CAPR-08-0107
© 2009 American Association for Cancer Research
Prevention of Tumorigenesis in p53-Null Mammary Epithelium by Rexinoid Bexarotene, Tyrosine Kinase Inhibitor Gefitinib, and Celecoxib
Daniel Medina1,
Frances Kittrell1,
Jamal Hill2,
Yun Zhang2,
Susan G. Hilsenbeck2,
Reid Bissonette3 and
Powel H. Brown2
Authors' Affiliations: 1 Department of Molecular and Cellular Biology and 2 Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas and 3 Ligand Pharmaceuticals, San Diego, California
Requests for reprints: Daniel Medina, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: 713-798-4483; Fax: 713-790-0545; E-mail: dmedina{at}bcm.edu.
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 in their response to the chemopreventive agents showed that mammary tumors arising from different oncogenic events will respond differently to the different agents.
Key Words: Research • prevention • mammary
This article has been cited by other articles:
|
|
|
|
 
M. C. Abba, Y. Hu, C. C. Levy, S. Gaddis, F. S. Kittrell, J. Hill, R. P. Bissonnette, P. H. Brown, D. Medina, and C. M. Aldaz
Identification of Modulated Genes by Three Classes of Chemopreventive Agents at Preneoplastic Stages in a p53-Null Mouse Mammary Tumor Model
Cancer Prevention Research,
February 1, 2009;
2(2):
175 - 184.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2009 by the American Association for Cancer Research.
