Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis
| Autor: | Sofi G. Julien, Yongxin Han, Brian P. Kennedy, Marilène Paquet, Nadia Dubé, Michel L. Tremblay, Michelle Read, Janice Penney, William J. Muller |
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| Rok vydání: | 2007 |
| Předmět: |
Genetically modified mouse
MAPK/ERK pathway Lung Neoplasms Receptor ErbB-3 MAP Kinase Signaling System Receptor ErbB-2 Molecular Sequence Data Mammary gland Down-Regulation Apoptosis Mice Transgenic Protein tyrosine phosphatase Biology medicine.disease_cause Mice Mammary Glands Animal Cell Line Tumor Genetics medicine Animals Lung Protein kinase B Mice Knockout Protein Tyrosine Phosphatase Non-Receptor Type 1 Mammary tumor Mammary Neoplasms Experimental Phenotype medicine.anatomical_structure Cancer research Female Protein Tyrosine Phosphatases Signal transduction Carcinogenesis Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Nature Genetics. 39:338-346 |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | We investigated the role of protein tyrosine phosphatase 1B (PTP1B) in mammary tumorigenesis using both genetic and pharmacological approaches. It has been previously shown that transgenic mice with a deletion mutation in the region of Erbb2 encoding its extracellular domain (referred to as NDL2 mice, for 'Neu deletion in extracellular domain 2') develop mammary tumors that progress to lung metastasis. However, deletion of PTP1B activity in the NDL2 transgenic mice either by breeding with Ptpn1-deficient mice or by treatment with a specific PTP1B inhibitor results in significant mammary tumor latency and resistance to lung metastasis. In contrast, specific overexpression of PTP1B in the mammary gland leads to spontaneous breast cancer development. The regulation of ErbB2-induced mammary tumorigenesis by PTB1B occurs through the attenuation of both the MAP kinase (MAPK) and Akt pathways. This report provides a rationale for the development of PTP1B as a new therapeutic target in breast cancer. |
| Databáze: | OpenAIRE |
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