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Pbx1 is required for Hox D3-mediated angiogenesis

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Abstract

Our previous studies showed that the homeobox (Hox) D3 transcription factor induces expression of αvβ3 integrin and promotes endothelial cell (EC) migration and angiogenesis. Since binding of Hox 3 factors to target DNA is enhanced by the co-factor Pbx, we investigated whether Pbx1 is also required for angiogenesis. We observed that EC predominantly express the Pbx1b isoform. Nuclear extracts from angiogenic EC express higher levels of active Pbx1 and more effectively form complexes on Pbx1/Hox consensus DNA oligonucleotides as compared to nuclear extracts from quiescent EC. Introduction of anti-sense against Pbx1 impaired the formation of Pbx1/Hox complexes on target DNA consensus in nuclear extracts from angiogenic EC. Anti-sense against Pbx1 also impaired EC migration and blocked angiogenesis induced by bFGF in vivo. Furthermore, although the levels of Hox D3 were unchanged, expression of its target gene, β3 integrin was reduced, consistent with impaired transcriptional activation by Hox D3. Together, these studies suggest that Pbx1 is required for pro-angiogenic Hox DNA binding and transcriptional activity in endothelial cells.

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Abbreviations

bFGF:

basic fibroblast growth factor

CAM:

chick chorioallantoic membrane

EC:

endothelial cells

HMEC-1:

human microvascular endothelial cells

Hox:

Homeobox

Pbx1:

pre B-cell leukemia transcription factor 1

Pbx1AS:

Pbx1 anti-sense

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Acknowledgements

This work is supported by a Grant from the NIH (CA85249) to NB and by post-doctoral fellowships from the California Breast Cancer Research Program (8FB-0013) to AC and (10FB-0166) to LE.

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Author notes

  1. A. Charboneau

    Present address: University of North Carolina, Chapel Hill, North Carolina, USA

Authors and Affiliations

  1. Department of Surgery, University of California, San Francisco, California, USA

    A. Charboneau, L. East, M. Rohde & N. Boudreau

  2. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA

    N. Mulholland

  3. University of California, Box 1302, San Francisco, CA, 94143, USA

    N. Boudreau

Authors
  1. A. Charboneau
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  2. L. East
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  3. N. Mulholland
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  4. M. Rohde
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  5. N. Boudreau
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Corresponding author

Correspondence to N. Boudreau.

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Charboneau, A., East, L., Mulholland, N. et al. Pbx1 is required for Hox D3-mediated angiogenesis. Angiogenesis 8, 289–296 (2006). https://doi.org/10.1007/s10456-005-9016-7

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  • DOI: https://doi.org/10.1007/s10456-005-9016-7

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