title: New experimental models for aromatase inhibitor resistance.
abstract: Clinical trials have demonstrated the importance of aromatase inhibitor (AI) therapy in the effective treatment of hormone-dependent breast cancers. In contrast to tamoxifen, an antagonist of the estrogen receptor (ER), AIs have shown to be better tolerated along with decreased recurrence rates of the disease. Currently, three third-generation AIs are being used: exemestane, letrozole, and anastrozole. Our laboratory is attempting to understand several aspects of AI functionality. In this paper, we first review recent findings from our structure-function studies of aromatase as well as the molecular characterization of the interaction between AIs and aromatase. Based on these studies, we propose new evidence for the interaction of letrozole and exemestane with aromatase. In addition, we will discuss recent results generated from our AI-resistant cell lines. Our laboratory has generated MCF-7aro cells that are resistant to letrozole, anastrozole, exemestane, and tamoxifen. Basic functional characterization of aromatase and ERalpha in these resistant cell lines has been done and microarray analysis has been employed in order to better understand the mechanism responsible for AI resistance on a genome-wide scale. The results generated so far suggest the presence of at least four types of resistant cell lines. Overall, the information presented in this paper supplements our understanding of AI function, and such information can be valuable for the development of treatment strategies against AI resistant breast cancers.
authors.affiliation: Department of Surgical Research, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. schen@coh.org
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
authors.forename: Selma
authors.initials: S
authors.lastname: Masri
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Hong
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Sheryl
authors.initials: S
authors.lastname: Phung
authors.forename: Yate-Ching
authors.initials: YC
authors.lastname: Yuan
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
mesh_terms: D001141:Aromatase / Q000737:chemistry / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D013629:Tamoxifen; D001141:Aromatase