Hypoxia-inducible factor-1α is a key regulator of metastasis in a transgenic model of cancer initiation and progression

Debbie Liao, Courtney Corle, Tiffany N. Seagroves, Randall S. Johnson

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)563-572
Number of pages10
JournalCancer Research
Volume67
Issue number2
DOIs
StatePublished - Jan 15 2007

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Hypoxia-Inducible Factor 1
Neoplasm Metastasis
Neoplasms
Breast
Epithelium
Growth
Breast Neoplasms
Heterografts
Transgenic Mice
Blood Vessels
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hypoxia-inducible factor-1α is a key regulator of metastasis in a transgenic model of cancer initiation and progression. / Liao, Debbie; Corle, Courtney; Seagroves, Tiffany N.; Johnson, Randall S.

In: Cancer Research, Vol. 67, No. 2, 15.01.2007, p. 563-572.

Research output: Contribution to journalArticle

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