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Abstract 482: The HER-2 erbB receptor is vital for growth of breast cancer cells in bone

Dawsey, Scott J. ; Ignatoski, Kathleen M. Woods ; Day, Kathleen C.

Cancer research (Chicago, Ill.), 2010-04, Vol.70 (8_Supplement), p.482-482 [Periódico revisado por pares]

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  • Título:
    Abstract 482: The HER-2 erbB receptor is vital for growth of breast cancer cells in bone
  • Autor: Dawsey, Scott J. ; Ignatoski, Kathleen M. Woods ; Day, Kathleen C.
  • É parte de: Cancer research (Chicago, Ill.), 2010-04, Vol.70 (8_Supplement), p.482-482
  • Descrição: Abstract HER-2 is a receptor tyrosine kinase that has been shown to be over expressed in 30% of human primary breast cancers (BrCa). Our animal model data and human bone met data, which we present here, indicates that HER-2 up-regulation is required for breast cancer cells to grow in and remodel bone. However, most bone metastases from BrCa will arise from a primary diagnosis of ER positive/HER-2 negative disease. We found that MCF-7 cells, an ER positive/HER-2 negative breast cancer model, formed tumors in bone that had up-regulated HER-2 protein expression. In order to directly test whether or not HER-2 expression has an affect on bone metastasis, we engineered a knock down of the HER-2 receptor in MCF-7 cells by utilizing a lentivirus plasmid containing the shRNA to the HER-2 receptor. Both the shRNA HER-2 knock-down and the vector-only control expressed the Green Fluorescence Protein (GFP) and puromycin resistance for plasmid selection. Our engineered MCF-7 control cells (shVector alone) or the HER-2 knock-down (shHER-2) were injected into the tibia of SCID mice. We found that both the vector-only and HER-2 knock-down cells grew tumors in mouse tibia. Anti-HER-2 immunohistochemical (IHC) analysis showed that the HER-2 protein was re-expressed in the knock down cells in tumors formed in tibiae. Additionally, we found that in eight patients with breast cancer bone metastasis, 100% of these cases contained a significant expression of HER-2 positive cells by IHC. As confirmation of our mouse studies, we found that all of the human bone biopsies obtained from ER positive/HER-2 negative disease were up-regulated for HER-2 in the bone microenvironment. Concomitant with our human data, MCF-7 cells required exogenous estrogen to form tumors in mammary fat pads and did not require exogenous estrogen to form tumors in bone. Therefore, we believe that BrCa cells can change, up-regulate protein expression of HER-2, and become estrogen independent in the bone microenvironment. It may be that these women could benefit from intervention with agents against HER-2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 482.
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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