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Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells

Oncogene volume 18, pages 1325–1332 (1999)Cite this article

Abstract

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.

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Acknowledgements

This research was supported in part by the UT MD Anderson Cancer Center Breast Cancer Research Program (to AMT) and the Gabriella Rich Leukemia Foundation (to GLB). We are very grateful for Alka Mehta's technical assistance.

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Authors and Affiliations

  1. Department of Bioimmunotherapy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Ana Maria Tari & Gabriel Lopez-Berestein

  2. Departments of Tumor Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Mien-Chie Hung & Kaiyi Li

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  1. Ana Maria Tari
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Tari, A., Hung, MC., Li, K. et al. Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. Oncogene 18, 1325–1332 (1999). https://doi.org/10.1038/sj.onc.1202422

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