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The type III TGF-beta receptor suppresses breast cancer progression.

Publication ,  Journal Article
Dong, M; How, T; Kirkbride, KC; Gordon, KJ; Lee, JD; Hempel, N; Kelly, P; Moeller, BJ; Marks, JR; Blobe, GC
Published in: J Clin Invest
January 2007

The TGF-beta signaling pathway has a complex role in regulating mammary carcinogenesis. Here we demonstrate that the type III TGF-beta receptor (TbetaRIII, or betaglycan), a ubiquitously expressed TGF-beta coreceptor, regulated breast cancer progression and metastasis. Most human breast cancers lost TbetaRIII expression, with loss of heterozygosity of the TGFBR3 gene locus correlating with decreased TbetaRIII expression. TbetaRIII expression decreased during breast cancer progression, and low TbetaRIII levels predicted decreased recurrence-free survival in breast cancer patients. Restoring TbetaRIII expression in breast cancer cells dramatically inhibited tumor invasiveness in vitro and tumor invasion, angiogenesis, and metastasis in vivo. TbetaRIII appeared to inhibit tumor invasion by undergoing ectodomain shedding and producing soluble TbetaRIII, which binds and sequesters TGF-beta to decrease TGF-beta signaling and reduce breast cancer cell invasion and tumor-induced angiogenesis. Our results indicate that loss of TbetaRIII through allelic imbalance is a frequent genetic event during human breast cancer development that increases metastatic potential.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

January 2007

Volume

117

Issue

1

Start / End Page

206 / 217

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Mice
  • Mammary Neoplasms, Animal
  • Immunology
  • Humans
  • Gene Expression Regulation, Neoplastic
 

Citation

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Dong, M., How, T., Kirkbride, K. C., Gordon, K. J., Lee, J. D., Hempel, N., … Blobe, G. C. (2007). The type III TGF-beta receptor suppresses breast cancer progression. J Clin Invest, 117(1), 206–217. https://doi.org/10.1172/JCI29293
Dong, Mei, Tam How, Kellye C. Kirkbride, Kelly J. Gordon, Jason D. Lee, Nadine Hempel, Patrick Kelly, Benjamin J. Moeller, Jeffrey R. Marks, and Gerard C. Blobe. “The type III TGF-beta receptor suppresses breast cancer progression.J Clin Invest 117, no. 1 (January 2007): 206–17. https://doi.org/10.1172/JCI29293.
Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, et al. The type III TGF-beta receptor suppresses breast cancer progression. J Clin Invest. 2007 Jan;117(1):206–17.
Dong, Mei, et al. “The type III TGF-beta receptor suppresses breast cancer progression.J Clin Invest, vol. 117, no. 1, Jan. 2007, pp. 206–17. Pubmed, doi:10.1172/JCI29293.
Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, Kelly P, Moeller BJ, Marks JR, Blobe GC. The type III TGF-beta receptor suppresses breast cancer progression. J Clin Invest. 2007 Jan;117(1):206–217.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

January 2007

Volume

117

Issue

1

Start / End Page

206 / 217

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Mice
  • Mammary Neoplasms, Animal
  • Immunology
  • Humans
  • Gene Expression Regulation, Neoplastic