The prolyl isomerase Pin1 induces LC-3 expression and mediates tamoxifen resistance in breast cancer.

ABSTRACT: Endocrine therapies, which inhibit estrogen receptor signaling, are the most common and effective treatments for estrogen receptoralpha-positive breast cancer. However, the utility of these agents is limited by the frequent development of resistance, and the precise mechanisms underlying endocrine therapy resistance remain incompletely understood. Here, we demonstrate that peptidyl-prolyl isomerase Pin1 is an important determinant of resistance to tamoxifen and show that Pin1 increases E2F-4- and Egr-1-driven expression of LC-3 as a result of an increased interaction with and phosphorylation of MEK1/2. In human tamoxifen-resistant breast cancer, our results show a significant correlation between Pin1 overexpression and high levels of LC-3. Promoter activity as well as expression levels of

SUBMITTER: Namgoong GM 

PROVIDER: S-EPMC2911270 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature