文章基本信息

标题：Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas
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作者：Saya H. Ebbesen ; Maurizio Scaltriti ; Carl U. Bialucha 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：11
页码：3030-3035
DOI：10.1073/pnas.1523693113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Loss of the tumor suppressor gene PTEN is implicated in breast cancer progression and resistance to targeted therapies, and is thought to promote tumorigenesis by activating PI3K signaling. In a transgenic model of breast cancer, Pten suppression using a tetracycline-regulatable short hairpin (sh)RNA cooperates with human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive and metastatic disease with elevated signaling through PI3K and, surprisingly, the mitogen-activated protein kinase (MAPK) pathway. Restoring Pten function is sufficient to down-regulate both PI3K and MAPK signaling and triggers dramatic tumor regression. Pharmacologic inhibition of MAPK signaling produces similar effects to Pten restoration, suggesting that the MAPK pathway contributes to the maintenance of advanced breast cancers harboring Pten loss.
关键词：breast cancer ; mouse models ; tumor suppressors ; RNAi ; targeted therapies