Elevated cyclic AMP suppresses ConA-induced MT1-MMP expression in MDA-MB-231 human breast cancer cells.
We have previously reported that induction of MMP-2 activation by Concanavalin A (ConA) in MDA-MB-231 human 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), and 3-isobutyl-1-methylxanthine (IBMX) partially inhibited ConA-induced MT1-MMP expression and MMP-2 activation 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.
Yu
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M
Department of Cell Biology, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Sato
H
H
Seiki
M
M
Spiegel
S
S
Thompson
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EW
D001943:Breast Neoplasms / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D015536:Down-Regulation; D004790:Enzyme Induction; D006801:Humans; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003208:Concanavalin A; D000242:Cyclic AMP; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases