Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1

Olga V. Volpert, Roberto Pili, Hashmat A. Sikder, Thomas Nelius, Tetiana Zaichuk, Chad Morris, Clinton B. Shiflett, Meghann K. Devlin, Katherine Conant, Rhoda M. Alani

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Id proteins are helix-loop-helix transcription factors that regulate tumor angiogenesis. In order to identify downstream effectors of Id1 involved in the regulation of angiogenesis, we performed PCR-select subtractive hybridization on wild-type and Id1 knockout mouse embryo fibroblasts (MEFs). Here we demonstrate that thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, is a target of transcriptional repression by Id1. We also show that Id1-null MEFs secrete an inhibitor of endothelial cell migration, which is completely inactivated by depletion of TSP-1. Furthermore, in vivo studies revealed decreased neovascularization in matrigel assays in Id1-null mice compared to their wild-type littermates. This decrease was completely reversed by a TSP-1 neutralizing antibody. We conclude that TSP-1 is a major target for Id1 effects on angiogenesis.

Original languageEnglish (US)
Pages (from-to)473-483
Number of pages11
JournalCancer Cell
Volume2
Issue number6
DOIs
StatePublished - Dec 2002

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Thrombospondin 1
Embryonic Structures
Fibroblasts
Angiogenesis Inhibitors
Neutralizing Antibodies
Knockout Mice
Cell Movement
Transcription Factors
Endothelial Cells
Polymerase Chain Reaction
Neoplasms
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Volpert, O. V., Pili, R., Sikder, H. A., Nelius, T., Zaichuk, T., Morris, C., ... Alani, R. M. (2002). Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. Cancer Cell, 2(6), 473-483. https://doi.org/10.1016/S1535-6108(02)00209-X

Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. / Volpert, Olga V.; Pili, Roberto; Sikder, Hashmat A.; Nelius, Thomas; Zaichuk, Tetiana; Morris, Chad; Shiflett, Clinton B.; Devlin, Meghann K.; Conant, Katherine; Alani, Rhoda M.

In: Cancer Cell, Vol. 2, No. 6, 12.2002, p. 473-483.

Research output: Contribution to journalArticle

Volpert, OV, Pili, R, Sikder, HA, Nelius, T, Zaichuk, T, Morris, C, Shiflett, CB, Devlin, MK, Conant, K & Alani, RM 2002, 'Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1', Cancer Cell, vol. 2, no. 6, pp. 473-483. https://doi.org/10.1016/S1535-6108(02)00209-X
Volpert, Olga V. ; Pili, Roberto ; Sikder, Hashmat A. ; Nelius, Thomas ; Zaichuk, Tetiana ; Morris, Chad ; Shiflett, Clinton B. ; Devlin, Meghann K. ; Conant, Katherine ; Alani, Rhoda M. / Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. In: Cancer Cell. 2002 ; Vol. 2, No. 6. pp. 473-483.
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