Adaptation to hypoxia is a critical step in tumor progression and is, in part, regulated by the transcription factor hypoxia-inducible factor-α (HIF-1α). Xenograft models have been extensively used to characterize the role of HIF-1α in experimental cancers. Although these models provide an understanding of tumor growth at terminal stages of malignancy, they do not address tumor initiation or metastatic progression. To elucidate these roles, HIF-1α was conditionally deleted in the mammary epithelium of a transgenic mouse model for metastatic breast cancer. Conditional deletion of HIF-1α in the mammary epithelium resulted in delayed tumor onset and retarded tumor growth; this was correlated with decreased tumor cell proliferation. Tumors with conditional deletion of HIF-1α were also less vascular during early tumor progression. Perhaps most surprisingly, deletion of HIF-1α in the mammary epithelium resulted in decreased pulmonary metastasis. These results show that whereas HIF-1α is not required for the initiation of breast tumor growth or tumor cell metastasis, the transcriptional activity of HIF-1α is a significant positive regulator of tumor progression and metastatic potential. © 2007 American Association for Cancer Research.
CITATION STYLE
Liao, D., Corle, C., Seagroves, T. N., & Johnson, R. S. (2007). Hypoxia-inducible factor-1α is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Research, 67(2), 563–572. https://doi.org/10.1158/0008-5472.CAN-06-2701
Mendeley helps you to discover research relevant for your work.