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- W2331058833 abstract "Breast cancer is the most common malignancy and the second most common cause of cancer related death in women. HER2+ over-expressing (HER2+) tumors comprise 20% to 25% of all cases and are associated with a poor prognosis. The discovery of HER2 monoclonal antibody-based therapeutics has greatly improved patient prognosis. However, patients suffer relapse and de novo resistance. Thus it is important to determine additional therapeutic targets in HER2+ breast cancer that might be used in combination with current therapies to improve patient survival. SHP2 (PTPN11) is a non-receptor protein-tyrosine phosphatase (PTP) that contains two SH2 domains at its N-terminus, a central PTP domain and a C-terminal proline-rich tail. Previous studies suggest that Shp2 is required for Ras/Erk signaling downstream of most growth factor receptors and integrins. Heterozygous germ-line PTPN11 mutations cause Noonan Syndrome and LEOPARD syndrome, which are associated with leukemia and cancer predisposition. Somatic PTPN11 mutations cause juvenile myelomonocytic leukemia (JMML) and several other neoplasms. We have discovered that Shp2 is required in Neu-mediated tumorigenesis in the MMTV-NIC mouse model; furthermore, SHP2-depleted human HER2+ BT-474 has defective tumorigenesis in nude mice. SHP2 is required in anchorage-independent growth in 4 HER2+ breast cancer cell lines, though its effect on growth on plastics appears minimal. I hypothesize that SHP2 is required for HER2+ breast tumor initiation and maintenance. I further hypothesize that SHP2 functions through specific substrates/interacting proteins in HER2+ breast cancer cells, possibly molecules that are involved in anchorage-independent proliferation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2150. doi:1538-7445.AM2012-2150" @default.
- W2331058833 created "2016-06-24" @default.
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- W2331058833 date "2012-04-15" @default.
- W2331058833 modified "2023-09-26" @default.
- W2331058833 title "Abstract 2150: The role of SHP2 in HER2+ breast cancer" @default.
- W2331058833 doi "https://doi.org/10.1158/1538-7445.am2012-2150" @default.
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