Correlation between the activation of Neu tyrosine kinase and promotion of foci formation induced by selected organochlorine compounds in the MCF-7 model system
✍ Scribed by Mariko Hatakeyama; Fumio Matsumura
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 94 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1095-6670
No coin nor oath required. For personal study only.
✦ Synopsis
Several studies have shown that some organochlorine compounds act like estrogen in certain animals and in vitro cell culture systems, and therefore, there is a possibility that they could promote the process of tumorigenesis in breast cancer cells. In our previous study, two representative organochlorines, 1,1,1trichloro 2-o-chlorophenyl-2-p-chlorophenyl ethane (o,p-DDT) and b-1,2,3,4,5,6-hexachlorocyclohexane (b-HCH), were found to directly activate the protein tyrosine kinase of Neu (c-erbB-2 proto-oncogene product) immunoprecipitates isolated from MCF-7 breast cancer cells. In the current study, we also found that 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) at 1 nM and ␣-HCH isomers at 100 nM could also significantly activate protein tyrosine kinase of Neu immunoprecipitates in a cell-free system. We also found that organochlorines result in an increase of Neu protein tyrosine kinase after intact cell treatment in estrogen-depleted medium. This Neu kinase activation by b-HCH (100 nM) was blocked when the cells were pretreated with Neu mRNA antisense oligonucleotide (p Ͻ 0.07, Student's t-test). Endogenously added ␣-, b-, and c-HCH, o,p-DDT, 2,2-dichlorobiphenyl (2,2-PCB), and 2,4,5-T at 100 nM were found to promote foci formation in postconfluent cultures of this cell line. This stimulatory effect caused by 17b-estradiol, o,p-DDT, and b-HCH on foci formation was inhibited by coincubation with Neu monoclonal antibody (p Ͻ 0.05). Those two events induced by organochlorines (i.e., Neu kinase activation and foci formation) seemed causally correlated.