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

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Stearns ME, Wang M, Sousa O

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

J Cell Sci. 1991 Jan;98 ( Pt 1):55-63.

PubMed ID

1647395 [ View in PubMed

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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 x 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Estramustine	Microtubule-associated protein 1A	Protein	Humans	Yes	Antagonist	Details
Estramustine	Microtubule-associated protein 2	Protein	Humans	Yes	Antagonist	Details