The estrogen-regulated protein, TFF1, stimulates migration of human breast cancer cells.

The human trefoil protein TFF1 is a small cysteine-rich secreted protein that is frequently expressed in breast tumors under the control of estrogen. The function of TFF1 in breast cancer is unknown. To test the hypothesis that it promotes tumor dissemination, we produced recombinant TFF1 and assessed its ability to stimulate the movement of breast cancer cells by using in vitro wounding and migration assays. Recombinant TFF1 stimulated migration at concentrations of TFF1 found in culture medium. Migration of MCF-7 breast cancer cells, which secrete TFF1, was stimulated by lower concentrations of TFF1 than MDA MB231 cells that do not produce TFF1. Dimeric TFF1, linked by a disulfide bond, and monomeric TFF1 are produced by estrogen-responsive breast cancer cell lines. Recombinant TFF1 dimer was eightfold more potent than TFF1 monomer, implying that the interaction of TFF1 with its receptor is facilitated by dimerization. The majority of TFF1-stimulated migration resulted from chemotaxis, but dimeric TFF1 stimulated some chemokinesis. These results show that estrogens can stimulate the motility of breast cancer cells via the induction of TFF1 and suggest that one reason for the efficacy of hormonal therapies is their ability to reduce expression of TFF1 and, hence, the migration of breast tumor cells.
AuthorsSara J Prest, Felicity E B May, Bruce R Westley
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 16 Issue 6 Pg. 592-4 (Apr 2002) ISSN: 1530-6860 [Electronic] United States
PMID11919164 (Publication Type: Journal Article)
Chemical References
  • Proteins
  • Receptors, Estrogen
  • TFF1 protein, human
  • Tumor Suppressor Proteins
  • Breast Neoplasms (chemistry, etiology, metabolism)
  • Chemotaxis (drug effects)
  • Dimerization
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Models, Biological
  • Protein Biosynthesis
  • Proteins (chemistry, pharmacology)
  • Receptors, Estrogen (analysis)
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins

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