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Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion
Journal article   Peer reviewed

Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion

M.E. Stearns, M. Wang and O. Sousa
Journal of cell science, v 98(1), pp 55-63
01 Jan 1991
DOI: https://doi.org/10.1242/jcs.98.1.55
PMID: 1647395
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Estramustine is a novel anti-microtubule drug shown to bind MAP-1 and MAP-2 (microtubule-associated proteins) in vitro. In this paper we have shown that estramustine specifically binds MAP-1A in Du 145a cells, resulting in disruption of MAP-1A microtubules and inhibition of type IV collagenase secretion. Immunofluorescence studies revealed that at 30 microM levels estramustine blocked type IV collagenase secretion by partial disruption of the MAP-1A microtubule networks. Immunoprecipitation studies with polyclonal antibodies provided quantitative evidence that 30–60 microM estramustine blocked secretion of a 105 × 10(3) Mr type IV collagenase. Pulse-labeling experiments confirmed that the effect was not a result of inhibition of either protein synthesis or altered rates of type IV collagenase turnover. Finally, drug uptake studies with [3H]estramustine, scintillation counting and fluorography demonstrated that the principal target of the drug was MAP-1A. For the first time we have shown that the drug blocks secretion by binding MAP-1A and causing incomplete disruption of the microtubule networks.

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Cell Biology
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