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Differential influence of antiestrogens on the in vitro release of gelatinases (type IV collagenases) by invasive and non-invasive breast cancer cells

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Abstract

Matrix metalloproteinases (MMPs) play an important role in tumor cell invasion and cancer metastasis. Accordingly, a higher level of these enzymes has been associated with the invasive phenotype. In the present study the effect of the antiestrogens, Analog II (AII), ICI-182,780 (ICI), and tamoxifen (TAM), on the in vitro release of MMPs, particularly gelatinases A and B by the MDA-MB-231 (MDA) and MCF-7 (MCF) human breast cancer cell lines was investigated using a solid-phase radioassay and substrate gel zymography. Quantitatively, the enzyme activity was found to be higher in the incubation medium from estrogen receptor (ER)-negative and more metastatic MDA cells compared to ER-positive and less metastatic MCF cells. Tissue inhibitor of metalloproteinases-1 (TIMP-1) reduced the enzyme activity in media from both MDA (56.36%) and MCF (71.03%) cells. Differential antiestrogen effects on the two cell lines were observed following 4 days of treatment of cells at a concentration of 10-6M. The enzyme activity from MDA cells was not influenced by treatment with any of the antiestrogens, whereas, in MCF cells, ICI produced the greatest enzyme inhibition (47.93%), followed by AII (36.51%) and TAM (24.05%). Concurrent treatment of MCF cells with 17-b-estradiol (10-9M) partially reversed the AII- and TAM-induced but did not alter ICI-induced inhibition of enzyme activity. Substrate gel zymography revealed that among the MMPs, the MDA cells released predominantly progelatinase A (72kDa) along with minor bands of activated forms, 62kDa and 59kDa, whereas progelatinase B (92kDa) was detected predominantly in the medium from MCF cells. Comparison of the overall antiestrogen effect indicates that ICI is the most potent inhibitor of enzyme activity in ER-positive MCF cells and that antiestrogen treatment may limit the metastatic potential of ER-positive breast cancer.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    S. M. Abbas Abidi, Eric W. Howard & J. Thomas Pento

  2. Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    John J. Dmytryk

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  1. S. M. Abbas Abidi
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  2. Eric W. Howard
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  3. John J. Dmytryk
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  4. J. Thomas Pento
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Abbas Abidi, S.M., Howard, E.W., Dmytryk, J.J. et al. Differential influence of antiestrogens on the in vitro release of gelatinases (type IV collagenases) by invasive and non-invasive breast cancer cells. Clin Exp Metastasis 15, 432–439 (1997). https://doi.org/10.1023/A:1018458406797

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