PMID: 9443065Jan 27, 1998Paper

Activation of c-Neu tyrosine kinase by o,p'-DDT and beta-HCH in cell-free and intact cell preparations from MCF-7 human breast cancer cells

Journal of Biochemical and Molecular Toxicology
E Enan, F Matsumura

Abstract

It has been suggested that there is a positive correlation between increased incidence of breast cancer and the presence of organochlorine residues such as DDT and HCH in breast tissues in the United States. To study possible biochemical links between these two parameters, we have examined the effect of o,p'-DDT, the most estrogenic congener of the DDT family of chemicals and beta-HCH on protein phosphorylation activities in MCF-7, a line derived from human breast cancer cells. Both of these organochlorine chemicals were found to be potent activators of protein kinases. Among kinases activated, protein tyrosine kinases (PTK) appear to be most affected as judged by the antagonistic action of genistein, a class-specific PTK inhibitor. Moreover, these organochlorines were found to activate PTK even under cell-free conditions, indicating that they are likely to interact directly with the target protein tyrosine kinase. As a result of immunoprecipitation with specific antibodies, and testing on the action of these organochlorines, we could show that the major kinase activated by o,p'-DDT is c-Neu (= c-erbB2 product protein). The concentrations of these organochlorines required to activate c-Neu were extremely low (0.1-1 nM range), w...Continue Reading

Citations

Sep 21, 2002·Journal of Biochemical and Molecular Toxicology·María G Moya de JuriAna M Pechen de D'Angelo
Feb 27, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·D M Tessier, F Matsumura
Jun 16, 2009·Journal of Biochemical and Molecular Toxicology·Gladis MagnarelliAna M Pechén de D'Angelo
Mar 3, 2004·Journal of Biochemical and Molecular Toxicology·María S SouzaAna M Pechén de D'Angelo
Jan 1, 2002·Environmental Toxicology and Pharmacology·Mariko HatakeyamaFumio Matsumura
Dec 18, 2004·Toxicology Letters·Daniel E FrigoJohn A McLachlan

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