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Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor).

Publication ,  Journal Article
Fen Li, C; Kandel, C; Baliko, F; Nadesan, P; Brünner, N; Alman, BA
Published in: Oncogene
February 24, 2005

Aggressive fibromatosis is a mesenchymal neoplasm associated with mutations, resulting in beta-catenin-mediated transcriptional activation. We found that plasminogen activator inhibitor-1 (PAI-1) was upregulated fourfold in aggressive fibromatosis. We investigated the ability of beta-catenin to regulate a PAI-1 reporter, and found that PAI-1 is an indirect target. To determine the role of PAI-1 in vivo, a mouse containing a targeted deletion in Pai-1 was crossed with a mouse that develops aggressive fibromatosis and gastrointestinal tumors (Apc/Apc1638N mouse). Pai-1 deficiency reduced the number of aggressive fibromatosis tumors formed, but not the number of gastrointestinal tumors. Deficiency of Pai-1 reduced tumor cell proliferation and motility rate. Although PAI-1 can alter cell motility by competing for a common binding site on vitronectin, blocking this site did not alter the motility rate. The number of cells moving through matrigel (invasion rate) did not change with Pai-1 deficiency, but because of the low motility rate the invasion index (invasion rate/motility) was increased in Pai-1-deficient cells. This suggests a proteolytic effect for PAI-1 regulating cell invasiveness. Our study found that, although PAI-1 has cellular effects that could inhibit or enhance tumor growth, on balance, it acts as a tumor enhancer in aggressive fibromatosis.

Duke Scholars

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

February 24, 2005

Volume

24

Issue

9

Start / End Page

1615 / 1624

Location

England

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Plasminogen Activator Inhibitor 1
  • Oncology & Carcinogenesis
  • Mice, Knockout
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Deletion
  • Fibromatosis, Aggressive
  • DNA Primers
 

Citation

APA
Chicago
ICMJE
MLA
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Fen Li, C., Kandel, C., Baliko, F., Nadesan, P., Brünner, N., & Alman, B. A. (2005). Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor). Oncogene, 24(9), 1615–1624. https://doi.org/10.1038/sj.onc.1208193
Fen Li, Catherine, Christopher Kandel, Frank Baliko, Puviindran Nadesan, Nils Brünner, and Benjamin A. Alman. “Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor).Oncogene 24, no. 9 (February 24, 2005): 1615–24. https://doi.org/10.1038/sj.onc.1208193.
Fen Li C, Kandel C, Baliko F, Nadesan P, Brünner N, Alman BA. Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor). Oncogene. 2005 Feb 24;24(9):1615–24.
Fen Li, Catherine, et al. “Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor).Oncogene, vol. 24, no. 9, Feb. 2005, pp. 1615–24. Pubmed, doi:10.1038/sj.onc.1208193.
Fen Li C, Kandel C, Baliko F, Nadesan P, Brünner N, Alman BA. Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor). Oncogene. 2005 Feb 24;24(9):1615–1624.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

February 24, 2005

Volume

24

Issue

9

Start / End Page

1615 / 1624

Location

England

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Plasminogen Activator Inhibitor 1
  • Oncology & Carcinogenesis
  • Mice, Knockout
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Deletion
  • Fibromatosis, Aggressive
  • DNA Primers