Control of Angiogenesis in Fibroblasts by p53 Regulation of Thrombospondin-1

Dameron, Kristina M.; Volpert, Olga V.; Tainsky, Michael A.; Bouck, Noël

doi:10.1126/science.7521539

Cited by 1,303 publications

(733 citation statements)

References 23 publications

Supporting

Mentioning

671

Contrasting

Unclassified

Order By: Relevance

“…67,68 The finding here, that the expression of neither TSP -1 nor IGF -BP3 is significantly altered in Av1p53 -treated cells, is in contrast to previous observations. 45,57,61,69 The discrepancy between these findings could be related to tissue specificity. We also noted that, similar to the results reported by Nishizaki et al 45 who used an Adv to transduce wtp53 into nonsmall cell lung cancer, there was no change in the mRNA level of bFGF.…”

Section: Discussionmentioning

confidence: 99%

Downmodulation of bFGF-binding protein expression following restoration of p53 function

et al. 2001

View full text Add to dashboard Cite

Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector -mediated wild -type p53 transduction results in growth inhibition of squamous cell carcinoma of the head and neck tumor cells both in vitro and in a xenograft mouse model. This growth inhibition is associated with the down -regulation of the expression of fibroblast growth factor binding protein, a secreted protein required for the activation of angiogenic factor basic FGF. These findings suggest that wtp53 -induced tumor regression is due, at least in part, to antiangiogenesis mediated by the downmodulation of fibroblast growth factor binding protein. Cancer Gene Therapy ( 2001 ) 8, 771 -782

show abstract

Section: Discussionmentioning

confidence: 99%

Downmodulation of bFGF-binding protein expression following restoration of p53 function

et al. 2001

View full text Add to dashboard Cite

show abstract

“…WT1 and p53 can interact physically (Maheswaran et al, 1993), and this interaction modulates their biological activities . p53 has been shown to positively regulate TSP1 synthesis (Dameron et al, 1994) but the promoter region responsible for this regulation has not been identi®ed. In this respect, it would be interesting to determine if p53 modulates the capacity of WT1 to repress TSP1 transcription.…”

Section: Repression Of Thrombospondin 1 Expression By Wt1mentioning

confidence: 99%

The Wilms' tumor gene product represses the transcription of thrombospondin 1 in response to overexpression of c-Jun

et al. 1999

View full text Add to dashboard Cite

“…p53 inhibits angiogenesis by at least three mechanisms: (1) by regulating expression and activity of the central regulator of hypoxia, the hypoxia-induced transcription factor-1a; (2) by inhibiting production of proangiogenic factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2); and (3) by increasing production of anti-angiogenic factors. 6,[9][10][11][12][13][14] p53 is able to induce tumour dormancy, and the loss of WTp53 reverses the tumour switch from a dormant non-angiogenic state to an angiogenic invasive phenotype. 15,16 Clinical data also suggest that p53 has a crucial role in controlling tumour vascularization.…”

Section: Introductionmentioning

confidence: 99%

The p53 isoform, Δ133p53α, stimulates angiogenesis and tumour progression

et al. 2012

View full text Add to dashboard Cite

The tumour suppressor p53, involved in DNA repair, cell cycle arrest and apoptosis, also inhibits blood vessel formation, that is, angiogenesis, a process strongly contributing to tumour development. The p53 gene expresses 12 different proteins (isoforms), including TAp53 (p53 (or p53a), p53b and p53g) and D133p53 isoforms (D133p53a, D133p53b and D133p53g). The D133p53a isoform was shown to modulate p53 transcriptional activity and is overexpressed in various human tumours. However, its role in tumour progression is still unexplored. In the present study, we examined the involvement of D133p53 isoforms in tumoural angiogenesis and tumour growth in the highly angiogenic human glioblastoma U87. Our data show that conditioned media from U87 cells depleted for D133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro. The D133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade. Furthermore, using conditioned media from U87 cells ectopically expressing each D133p53 isoform, we determined that D133p53a and D133p53g but not D133p53b, stimulate angiogenesis. Our in vivo data using the chicken chorio-allantoic membrane and mice xenografts establish that angiogenesis and growth of glioblastoma U87 tumours are inhibited upon depletion of D133p53 isoforms. By TaqMan low-density array, we show that alteration of expression ratio of D133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with D133p53 isoforms inducing pro-angiogenic gene expression and repressing anti-angiogenic gene expression.

show abstract

Control of Angiogenesis in Fibroblasts by p53 Regulation of Thrombospondin-1

Cited by 1,303 publications

References 23 publications

Downmodulation of bFGF-binding protein expression following restoration of p53 function

Downmodulation of bFGF-binding protein expression following restoration of p53 function

The Wilms' tumor gene product represses the transcription of thrombospondin 1 in response to overexpression of c-Jun

The p53 isoform, Δ133p53α, stimulates angiogenesis and tumour progression

Contact Info

Product

Resources

About