Skip to main content

The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer.

Publication ,  Journal Article
Turley, RS; Finger, EC; Hempel, N; How, T; Fields, TA; Blobe, GC
Published in: Cancer Res
February 1, 2007

The transforming growth factor-beta (TGF-beta) signaling pathway has an important role in regulating normal prostate epithelium, inhibiting proliferation, differentiation, and both androgen deprivation-induced and androgen-independent apoptosis. During prostate cancer formation, most prostate cancer cells become resistant to these homeostatic effects of TGF-beta. Although the loss of expression of either the type I (TbetaRI) or type II (TbetaRII) TGF-beta receptor has been documented in approximately 30% of prostate cancers, most prostate cancers become TGF-beta resistant without mutation or deletion of TbetaRI, TbetaRII, or Smads2, 3, and 4, and thus, the mechanism of resistance remains to be defined. Here, we show that type III TGF-beta receptor (TbetaRIII or betaglycan) expression is decreased or lost in the majority of human prostate cancers as compared with benign prostate tissue at both the mRNA and protein level. Loss of TbetaRIII expression correlates with advancing tumor stage and a higher probability of prostate-specific antigen (PSA) recurrence, suggesting a role in prostate cancer progression. The loss of TbetaRIII expression is mediated by the loss of heterozygosity at the TGFBR3 genomic locus and epigenetic regulation of the TbetaRIII promoter. Functionally, restoring TbetaRIII expression in prostate cancer cells potently decreases cell motility and cell invasion through Matrigel in vitro and prostate tumorigenicity in vivo. Taken together, these studies define the loss of TbetaRIII expression as a common event in human prostate cancer and suggest that this loss is important for prostate cancer progression through effects on cell motility, invasiveness, and tumorigenicity.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

February 1, 2007

Volume

67

Issue

3

Start / End Page

1090 / 1098

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Loss of Heterozygosity
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Turley, R. S., Finger, E. C., Hempel, N., How, T., Fields, T. A., & Blobe, G. C. (2007). The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer. Cancer Res, 67(3), 1090–1098. https://doi.org/10.1158/0008-5472.CAN-06-3117
Turley, Ryan S., Elizabeth C. Finger, Nadine Hempel, Tam How, Timothy A. Fields, and Gerard C. Blobe. “The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer.Cancer Res 67, no. 3 (February 1, 2007): 1090–98. https://doi.org/10.1158/0008-5472.CAN-06-3117.
Turley RS, Finger EC, Hempel N, How T, Fields TA, Blobe GC. The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer. Cancer Res. 2007 Feb 1;67(3):1090–8.
Turley, Ryan S., et al. “The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer.Cancer Res, vol. 67, no. 3, Feb. 2007, pp. 1090–98. Pubmed, doi:10.1158/0008-5472.CAN-06-3117.
Turley RS, Finger EC, Hempel N, How T, Fields TA, Blobe GC. The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer. Cancer Res. 2007 Feb 1;67(3):1090–1098.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

February 1, 2007

Volume

67

Issue

3

Start / End Page

1090 / 1098

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Loss of Heterozygosity