Expression of the PAX8/PPARγ fusion protein is associated with decreased neovascularization in vivo: Impact on tumorigenesis and disease prognosis

H. V. Reddi, P. Madde, L. A. Marlow, John A III Copland, B. McIver, S. K G Grebe, N. L. Eberhardt

Research output: Contribution to journalArticle

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Abstract

The PAX8/PPARγ fusion protein (PPFP) occurs in 36% of human follicular thyroid carcinoma (FTC) and is associated with favorable prognosis. To elucidate the function of PPFP in FTC, we analyzed the consequences of PPFP expression in immortalized thyrocytes in vitro and in vivo via xenograft tumorigenesis. While PPFP-expressing cells exhibited oncogenic hallmarks, including increased growth and decreased apoptosis, in vitro, xenograft tumors were initiated but not sustained in vivo. PPFP xenograft tumors exhibited reduced CD31 staining and VEGF expression, suggesting that PPFP modulates neovascularization. Microarray analysis demonstrated increased expression of tissue inhibitor of metalloproteinase (TIMP-3), an inhibitor of angiogenesis, in PPFP cells and tumors, a finding confirmed by quantitative PCR and immunohistochemistry. Immunohistochemical staining of archival human thyroid tumors demonstrates a significant decrease in CD31 staining in all adenomas and carcinomas containing the PAX8/PPARγ rearrangement. Decreased angiogenesis in PPFP-containing tumors is directly correlated with our observations in the xenograft model and provides evidence for the first time that PPFP may impact FTC tumorigenesis by modulating angiogenesis in vivo.

Original languageEnglish (US)
Pages (from-to)480-492
Number of pages13
JournalGenes and Cancer
Volume1
Issue number5
DOIs
StatePublished - 2010

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Peroxisome Proliferator-Activated Receptors
Carcinogenesis
Follicular Adenocarcinoma
Proteins
Heterografts
Tissue Inhibitor of Metalloproteinase-3
Neoplasms
Staining and Labeling
Angiogenesis Inhibitors
Cell Fusion
Microarray Analysis
Adenoma
Vascular Endothelial Growth Factor A
Thyroid Gland
Immunohistochemistry
Apoptosis
Carcinoma
Polymerase Chain Reaction

Keywords

  • Angiogenesis
  • Follicular thyroid carcinoma
  • Neovascularization
  • PAX8/PPARγ fusion protein
  • Tumor suppressor
  • Xenograft tumors

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Expression of the PAX8/PPARγ fusion protein is associated with decreased neovascularization in vivo : Impact on tumorigenesis and disease prognosis. / Reddi, H. V.; Madde, P.; Marlow, L. A.; Copland, John A III; McIver, B.; Grebe, S. K G; Eberhardt, N. L.

In: Genes and Cancer, Vol. 1, No. 5, 2010, p. 480-492.

Research output: Contribution to journalArticle

Reddi, H. V. ; Madde, P. ; Marlow, L. A. ; Copland, John A III ; McIver, B. ; Grebe, S. K G ; Eberhardt, N. L. / Expression of the PAX8/PPARγ fusion protein is associated with decreased neovascularization in vivo : Impact on tumorigenesis and disease prognosis. In: Genes and Cancer. 2010 ; Vol. 1, No. 5. pp. 480-492.
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