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beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds.

Publication ,  Journal Article
Cheon, SS; Cheah, AYL; Turley, S; Nadesan, P; Poon, R; Clevers, H; Alman, BA
Published in: Proc Natl Acad Sci U S A
May 14, 2002

Fibroproliferative processes are a group of disorders in which there is excessive proliferation of spindle (mesenchymal fibroblast-like) cells. They range from hypertrophic scars to neoplasms such as aggressive fibromatosis. Cells from these disorders share cytologic similarity with fibroblasts present during the proliferative phase of wound healing, suggesting that they represent a prolonged wounding response. A critical role for beta-catenin in mesenchymal cells in fibroproliferative processes is suggested by its high rate of somatic mutation in aggressive fibromatosis. Using a Tcf-reporter mouse we found that beta-catenin protein level and Tcf-transcriptional activity are elevated in fibroblasts during the proliferative phase of healing. We generated a transgenic mouse in which stabilized beta-catenin is expressed in mesenchymal cells under control of a tetracycline-regulated promoter. Fibroblasts from the transgenic mice exhibited increased proliferation, motility, and invasiveness when expressing stabilized beta-catenin and induced tumors after induction of the transgene when grafted into nude mice. Mice developed aggressive fibromatoses and hyperplastic gastrointestinal polyps after 3 months of transgene induction and healed with hyperplastic cutaneous wounds compared with control mice, which demonstrates an important function for beta-catenin in mesenchymal cells and shows a central role for beta-catenin in wound healing and fibroproliferative disorders.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 14, 2002

Volume

99

Issue

10

Start / End Page

6973 / 6978

Location

United States

Related Subject Headings

  • beta Catenin
  • Wounds and Injuries
  • Wound Healing
  • Transcriptional Activation
  • Trans-Activators
  • Skin
  • Mice, Transgenic
  • Mice, Nude
  • Mice
  • Mesoderm
 

Citation

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Cheon, S. S., Cheah, A. Y. L., Turley, S., Nadesan, P., Poon, R., Clevers, H., & Alman, B. A. (2002). beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci U S A, 99(10), 6973–6978. https://doi.org/10.1073/pnas.102657399
Cheon, Sophia S., Alexander Y. L. Cheah, Stefanie Turley, Puviindran Nadesan, Raymond Poon, Hans Clevers, and Benjamin A. Alman. “beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds.Proc Natl Acad Sci U S A 99, no. 10 (May 14, 2002): 6973–78. https://doi.org/10.1073/pnas.102657399.
Cheon SS, Cheah AYL, Turley S, Nadesan P, Poon R, Clevers H, et al. beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6973–8.
Cheon, Sophia S., et al. “beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds.Proc Natl Acad Sci U S A, vol. 99, no. 10, May 2002, pp. 6973–78. Pubmed, doi:10.1073/pnas.102657399.
Cheon SS, Cheah AYL, Turley S, Nadesan P, Poon R, Clevers H, Alman BA. beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6973–6978.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 14, 2002

Volume

99

Issue

10

Start / End Page

6973 / 6978

Location

United States

Related Subject Headings

  • beta Catenin
  • Wounds and Injuries
  • Wound Healing
  • Transcriptional Activation
  • Trans-Activators
  • Skin
  • Mice, Transgenic
  • Mice, Nude
  • Mice
  • Mesoderm