In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 67, No. 24 ( 2007-12-15), p. 11742-11750
Abstract:
Exposure to and bioaccumulation of lipophilic environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs), has been implicated in breast cancer. Treatment of female rats with the prototypic xenobiotic PAH 7,12-dimethylbenz(a)anthracene (DMBA) induces mammary tumors with an invasive phenotype. Here, we show that green tea prevents or reverses loss of the epithelial marker E-cadherin on the surface of DMBA-induced in situ cancers. To investigate the mechanism(s) leading to a less invasive phenotype, the effects of the green tea polyphenol epigallocatechin-3 gallate (EGCG) on mammary tumor cells were assessed. EGCG reversed epithelial to mesenchymal transition (EMT) in DMBA-treated NF-κB c-Rel–driven mammary tumor cells and reduced levels of c-Rel and the protein kinase CK2. Ectopic coexpression of c-Rel and CK2α in untransformed mammary epithelial cells was sufficient to induce a mesenchymal gene profile. Mammary tumors and cell lines derived from MMTV-c-Rel × CK2α bitransgenic mice displayed a highly invasive phenotype. Coexpression of c-Rel and CK2, or DMBA exposure induced the aryl hydrocarbon receptor (AhR) and putative target gene product Slug, an EMT master regulator, which could be reversed by EGCG treatment. Thus, activation of c-Rel and CK2 and downstream targets AhR and Slug by DMBA induces EMT; EGCG can inhibit this signaling. [Cancer Res 2007;67(24):11742–50]
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-07-2730
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2007
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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