Journal
SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-46776-7
Keywords
-
Categories
Funding
- University of Buenos Aires -Argentina [UBACYT 2017-20020160100099BA]
- National Agency for Scientific and Technological Promotion, MinCyT - Argentina [PICT-2014-0972]
- National Institute of Cancer (INC)
- National Scientific and Technical Research Council (CONICET) - Argentina, P.U.E [22920160100062]
Ask authors/readers for more resources
Acyl-CoA synthetase 4 (ACSL4) overexpression plays a causal role in the aggressiveness of triple negative breast cancer. In turn, a negative correlation has been established between ACSL4 and estrogen receptor alpha (ER alpha) expression. However, the upstream regulatory mechanisms leading to differential ACSL4 expression between triple negative breast cancer and ER alpha-positive cells remained unknown. We performed the characterization of the human ACSL4 promoter and the identification of transcription factors involved. Deletional analysis demonstrated the proximal 43 base pairs of the promoter are involved in overexpression. By site directed mutagenesis we describe that retinoid-related orphan receptor alpha (ROR alpha), Sp1 and E2F elements are involved in the promoter activity. We established for the first time that estrogen-related receptor alpha (ERR alpha) is a transcription factor involved in the higher activation of the human ACSL4 promoter in breast cancer cells. Furthermore, a combination of inhibitors of ACSL4 and ERR alpha produced a synergistic decrease in MDA-MB-231 cell proliferation. We also demonstrated that ER alpha restoration in triple negative breast cancer cells downregulates ACSL4 expression. The results presented in this manuscript demonstrated transcriptional mechanism is involved in the different expression of ACSL4 in human breast cancer cell lines of different aggressiveness.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available