Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas

Ebbesen, S. H., Scaltriti, M., Bialucha, C. U., Morse, N., Kastenhuber, E. R., Wen, H. Y., Dow, L. E., Baselga, J., Lowe, S. W. (March 2016) Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas. Proc Natl Acad Sci U S A, 113 (11). pp. 3030-3035. ISSN 1091-6490 (Electronic)0027-8424 (Linking)

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DOI: 10.1073/pnas.1523693113


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.

Item Type: Paper
Uncontrolled Keywords: RNAi breast cancer mouse models targeted therapies tumor suppressors
Subjects: therapies > gene therapy
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
diseases & disorders > cancer > cancer types > breast cancer
CSHL Authors:
Communities: School of Biological Sciences > Publications
Depositing User: Matt Covey
Date: 15 March 2016
Date Deposited: 09 Mar 2016 16:17
Last Modified: 08 Nov 2017 20:04
PMCID: PMC4801318
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