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Elevated cyclic AMP suppresses ConA-induced MT1-MMP expression in MDA-MB-231 human breast cancer cells

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Abstract

We have previously reported that induction of MMP-2 activation by Concanavalin A (ConA) in MDA-MB-231human breast cancer cells involves both transcriptional and post-transcriptional mechanisms, and that the continuous presence of ConA is required for MMP-2 activation (Yu et al. Cancer Res, 55, 3272-7, 1995).In an effort to identify signal transduction pathways which may either contribute to or modulate this mechanism,we found that three different cAMP-inducing agents, cholera toxin (CT), forskolin (FSK), and3-isobutyl-1-methylxanthine (IBMX) partially inhibited ConA-induced MT1-MMP expression and MMP-2activation in MDA-MB-231 cells. Combinations of CT or FSK with IBMX exhibited additive effects on reduction of MT1-MMP mRNA expression and MMP-2 activation. Agents which increase cAMP levels appeared to target transcriptional aspects of ConA induction, reducing MT1-MMP mRNA and protein in parallel with the reduced MMP-2 activation. In the absence of ConA, down-regulation of constitutive production of MT1-MMP mRNA and protein was observed, indicating that cAMP acts independently of ConA. These observations may help to elucidate factors regulating MT1-MMP expression, which may be pivotal to the elaboration of invasive machinery on the cell surface. © Rapid Science 1998

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Authors and Affiliations

  1. Department of Cell Biology, Georgetown University Medical Center NW, Washington DC, USA

    Ming Yu

  2. Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Ishikawa, 920, Japan

    Hiroshi Sato

  3. Department of Biochemistry and Molecular Biology, Georgetown University Medical Center NW, Washington DC, USA

    Motoharu Seiki

  4. Vincent T. Lombardi Cancer Center, Georgetown University Medical Center NW, Washington DC, USA

    Sarah Spiegel

  5. Department of Orthopedic Surgery, Georgetown University Medical Center NW, Washington DC, USA

    Erik W. Thompson

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  1. Ming Yu
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  2. Hiroshi Sato
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  3. Motoharu Seiki
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  4. Sarah Spiegel
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  5. Erik W. Thompson
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Yu, M., Sato, H., Seiki, M. et al. Elevated cyclic AMP suppresses ConA-induced MT1-MMP expression in MDA-MB-231 human breast cancer cells. Clin Exp Metastasis 16, 185–191 (1998). https://doi.org/10.1023/A:1006580406314

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