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Abstract #0528

Breast cancer cells can be rescued by Matrigel from the growth inhibitory effects of HIF-1α and HIF-2α silencing

Santosh Kumar Bharti 1 , Balaji Krishnamachary 1 , Wenlian Zhu 1 , Flonne Wildes 1 , Samata M Kakkad 1 , Yelena Mironchik 1 , Dmitri Artemov 1 , and Zaver M Bhujwalla 1

1 Div. of Cancer Imaging Research, The Russell H. Morgan Dept. of Radiology and Radiological science, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States

The heterodimeric transcription factors HIF-1/2 play an important role in driving angiogenesis by increasing the expression of vascular endothelial growth factor (VEGF) in hypoxic tumor microenvironments. Here we genetically modified the aggressive breast cancer cell line MDA-MB-231 to expresses short hairpin RNA that silences both isoforms of HIF (HIF-1α and HIF-2α). We found increased vascular permeability in HIF-1 and 2α silenced tumors compared to empty vector tumors, together with a growth advantage in the presence of Matrigel co-inoculated in the mammary fat pad. These data demonstrate the importance of the extracellular matrix in modulating outcomes of molecular pathway modifications.

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