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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