title: The effect of antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells.
abstract: BACKGROUND
  In a previous study we compared the influence of several growth factors on cancer cells in culture and observed that transforming growth factor-beta (TGF-beta) enhanced the invasiveness of several breast cancer cell lines. The objective of the present study was to determine the influence of three unique antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells.
  
  
  METHODS
  The chemotactic activity of TGF-beta was assayed in vitro using collagen IV-coated transwell chambers with either MCF-7 or MDA-MB-231 human breast cancer cells. The cells were pretreated with antiestrogen for 4 days, harvested and placed in the upper transwell chamber. TGF-beta was added to the lower chamber and cell migration and collagenase release were determined following a 6-hour incubation.
  
  
  RESULTS
  In this study TGF-beta enhanced the chemotaxis of both cell types with a much greater effect on the MDA-MB-231 cells. However, TGF-beta-mediated chemotaxis of the MCF-7 cells was inhibited by antiestrogen pretreatment while TGF-beta-mediated chemotaxis of the MDA-MB-231 cells was not altered. Further, neither TGF-beta nor antiestrogen treatment altered collagenase release from either cell line.
  
  
  CONCLUSIONS
  The data demonstrate that pure antiestrogens are capable of inhibiting TGF-beta-mediated chemotaxis in estrogen receptor (ER)-positive breast cancer cells by a mechanism which is independent of collagenase release. Finally, the results of this study suggest a coupling of the TGF-beta and ER signaling pathways and indicate that TGF-beta may be an important therapeutic target for the treatment or inhibition of breast cancer metastasis.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma, Health Sciences Center, Oklahoma City 73117, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Tong
authors.forename: Talitha T
authors.initials: TT
authors.lastname: Rajah
authors.forename: Xiao Ping
authors.initials: XP
authors.lastname: Zang
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Pento
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002633:Chemotaxis / Q000187:drug effects*; D017364:Collagenases / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D000077267:Fulvestrant; D006801:Humans; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; C035174:tamoxifen analog II; D017364:Collagenases