ArticleProceedings of the National Academy of Sciences of the United States of America2000
Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-alpha bigenic mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 128 citations in OpenAlex.
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- Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Targeting the HER/EGFR/ErbB family to prevent breast cancer.Cancer prevention research (Philadelphia, Pa.) · 2011Review
- Loss of BRCA1 leads to an increase in epidermal growth factor receptor expression in mammary epithelial cells, and epidermal growth factor receptor inhibition prevents estrogen receptor-negative cancers in BRCA1-mutant mice.Breast cancer research : BCR · 2011Article
- Oncogenes and tumor suppressor genes.Cold Spring Harbor perspectives in biology · 2010Review
- Brain injury expands the numbers of neural stem cells and progenitors in the SVZ by enhancing their responsiveness to EGF.ASN neuro · 2009Article
- Proteasome-mediated degradation and functions of hematopoietic progenitor kinase 1 in pancreatic cancer.Cancer research · 2009Article
- Prevention of ER-negative breast cancer.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2009Review
- Improvement of sensitivity to tamoxifen in estrogen receptor-positive and Herceptin-resistant breast cancer cells.Journal of molecular endocrinology · 2008Article
- Chronic pharmacologic inhibition of EGFR leads to cardiac dysfunction in C57BL/6J mice.Toxicology and applied pharmacology · 2008Article
- Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway.Leukemia · 2008Article
- Transgenic models to study actions of prolactin in mammary neoplasia.Journal of mammary gland biology and neoplasia · 2008Review
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Overexpression of ErbB-2/Neu has been causally associated with mammary epithelial transformation. Here we report that blockade of the epidermal growth factor receptor (EGFR) kinase with AG-1478 markedly delays breast tumor formation in mouse mammary tumor virus (MMTV)/Neu + MMTV/transforming growth factor alpha bigenic mice. This delay was associated with inhibition of EGFR and Neu signaling, reduction of cyclin-dependent kinase 2 (Cdk2) and mitogen-activated protein kinase (MAPK) activities and cyclin D1, and an increase in the levels of the Cdk inhibitor p27(Kip1). In addition, BrdUrd incorporation into tumor cell nuclei was prevented with no signs of tumor cell apoptosis. These observations prompted us to investigate the stability of p27. Recombinant p27 was degraded rapidly in vitro by untreated but not by AG-1478-treated tumor lysates. Proteasome depletion of the tumor lysates, addition of the specific MEK1/2 inhibitor U-0126, or a T187A mutation in recombinant p27 all prevented p27 degradation. Cdk2 and MAPK precipitates from untreated tumor lysates phosphorylated recombinant wild-type p27 but not the T187A mutant in vitro. Cdk2 and MAPK precipitates from AG-1478-treated tumors were unable to phosphorylate p27 in vitro. These data suggest that increased signaling by ErbB receptors up-regulates MAPK activity, which, in turn, phosphorylates and destabilizes p27, thus contributing to dysregulated cell cycle progression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.