Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas Journal Article
| Authors: | Ebbesen, S. H.; Scaltriti, M.; Bialucha, C. U.; Morse, N.; Kastenhuber, E. R.; Wen, H. Y.; Dow, L. E.; Baselga, J.; Lowe, S. W. |
| Article Title: | Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas |
| Abstract: | 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 tetracyclineregulatable short hairpin (sh)RNA cooperateswith human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive andmetastatic 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. |
| Keywords: | breast cancer; mouse models; tumor suppressors; targeted therapies; rnai |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 113 |
| Issue: | 11 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2016-03-15 |
| Start Page: | 3030 |
| End Page: | 3035 |
| Language: | English |
| DOI: | 10.1073/pnas.1523693113 |
| PROVIDER: | scopus |
| PMCID: | PMC4801318 |
| PUBMED: | 26929372 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2016 -- Source: Scopus |
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