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  • Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells.

Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells.

Molecular carcinogenesis (2014-10-21)
Yan Zhuang, Hong T Nguyen, Matthew E Burow, Ying Zhuo, Samir S El-Dahr, Xiao Yao, Subing Cao, Erik K Flemington, Kenneth P Nephew, Fang Fang, Bridgette Collins-Burow, Lyndsay V Rhodes, Qiang Yu, Janarthanan Jayawickramarajah, Bin Shan
ZUSAMMENFASSUNG

Epigenetic regulation of gene expression is critical to phenotypic maintenance and transition of human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) is a long intergenic non-coding RNA that epigenetically represses gene expression via recruitment of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase. Elevated expression of HOTAIR promotes progression of breast cancer. In the current study we examined the expression and function of HOTAIR in MCF-7-TNR cells, a derivative of the luminal-like breast cancer cell line MCF-7 that acquired resistance to TNF-α-induced cell death. The expression of HOTAIR, markers of the luminal-like and basal-like subtypes, and growth were compared between MCF-7 and MCF-7-TNR cells. These variables were further assessed upon inhibition of HOTAIR, EZH2, p38 MAPK, and SRC kinase in MCF-7-TNR cells. When compared with MCF-7 cells, MCF-7-TNR cells exhibited an increase in the expression of HOTAIR, which correlated with characteristics of a luminal-like to basal-like transition as evidenced by dysregulated gene expression and accelerated growth. MCF-7-TNR cells exhibited reduced suppressive histone H3 lysine27 trimethylation on the HOTAIR promoter. Inhibition of HOTAIR and EZH2 attenuated the luminal-like to basal-like transition in terms of gene expression and growth in MCF-7-TNR cells. Inhibition of p38 and SRC diminished HOTAIR expression and the basal-like phenotype in MCF-7-TNR cells. HOTAIR was robustly expressed in the native basal-like breast cancer cells and inhibition of HOTAIR reduced the basal-like gene expression and growth. Our findings suggest HOTAIR-mediated regulation of gene expression and growth associated with the basal-like phenotype of breast cancer cells.

MATERIALIEN
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Produktbeschreibung

Sigma-Aldrich
ChIPAb+-Trimethyl-Histon H3 (Lys27) - durch ChIP validiertes Antikörper- und Primer-Set, from rabbit, purified by using Protein A
Sigma-Aldrich
Anti-Cytokeratin 8 Antibody, clone 4.1.18, clone 4.1.18, Chemicon®, from mouse
Sigma-Aldrich
Anti-HOXC11 (AB2) antibody produced in rabbit, IgG fraction of antiserum