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Expression of the aryl hydrocarbon receptor is not required for the proliferation, migration, invasion, or estrogen‐dependent tumorigenesis of MCF‐7 breast cancer cells
Author(s) -
Spink Barbara C.,
Bennett James A.,
Lostritto Nicole,
Cole Jacquelyn R.,
Spink David C.
Publication year - 2013
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.21889
Subject(s) - aryl hydrocarbon receptor , biology , carcinogenesis , cell growth , cancer research , mcf 7 , estrogen receptor , transcription factor , cancer cell , aryl hydrocarbon receptor nuclear translocator , microbiology and biotechnology , cancer , breast cancer , biochemistry , gene , human breast , genetics
The AhR was initially identified as a ligand‐activated transcription factor mediating effects of chlorinated dioxins and polycyclic aromatic hydrocarbons on cytochrome P450 1 (CYP1) expression. Recently, evidence supporting involvement of the AhR in cell‐cycle regulation and tumorigenesis has been presented. To further define the roles of the AhR in cancer, we investigated the effects of AhR expression on cell proliferation, migration, invasion, and tumorigenesis of MCF‐7 human breast cancer cells. In these studies, the properties of MCF‐7 cells were compared with those of two MCF‐7‐derived sublines: AH R100 , which express minimal AhR, and AhR exp , which overexpress AhR. Quantitative PCR, Western immunoblots, 17β‐estradiol (E 2 ) metabolism assays, and ethoxyresorufin O ‐deethylase assays showed the lack of AhR expression and AhR‐regulated CYP1 expression in AH R100 cells, and enhanced AhR and CYP1 expression in AhR exp cells. In the presence of 1 nM E 2 , rates of cell proliferation of the three cell lines showed an inverse correlation with the levels of AhR mRNA. In comparison with MCF‐7 and AhR exp cells, AH R100 cells produced more colonies in soft agar and showed enhanced migration and invasion in chamber assays with E 2 as the chemoattractant. Despite the lack of significant AhR expression, AH R100 cells retained the ability to form tumors in severe combined immunodeficient mice when supplemented with E 2 , producing mean tumor volumes comparable to those observed with MCF‐7 cells. These studies indicate that, while CYP1 expression and inducibility are highly dependent on AhR expression, the proliferation, invasion, migration, anchorage‐independent growth, and estrogen‐stimulated tumor formation of MCF‐7 cells do not require the AhR. © 2012 Wiley Periodicals, Inc.