Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2019 Feb 5;509(2):476-482. doi: 10.1016/j.bbrc.2018.12.145. Epub 2018 Dec 27.

Overexpression of the steroidogenic acute regulatory protein in breast cancer: Regulation by histone deacetylase inhibition.

Author information

1
Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, 79430, USA. Electronic address: pulak.manna@ttuhsc.edu.
2
Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, 79430, USA.
3
Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, 79430, USA. Electronic address: kevin.pruitt@ttuhsc.edu.

Abstract

Dysregulation of steroid biosynthesis has been implicated in the pathophysiology of a variety of cancers. One such common malignancy in women is breast cancer that is frequently promoted by estrogen overproduction. All steroid hormones are made from cholesterol, and the rate-limiting step in steroid biosynthesis is primarily mediated by the steroidogenic acute regulatory (StAR) protein. Whereas the involvement of StAR in the regulation steroid hormone biosynthesis is well established, its association to breast cancer remains obscure. Herein, we report that estrogen receptor positive breast cancer cell lines (MCF7, MDA-MB-361, and T-47D) displayed aberrant high expression of the StAR protein, concomitant with 17β-estradiol (E2) synthesis, when compared their levels with normal mammary epithelial (MCF10A and MCF12F) and triple negative breast cancer (MDA-MB-468, MDA-MB-231, and BT-549) cells. StAR was identified as a novel acetylated protein in MCF7 cells, in which liquid chromatography-tandem mass spectrometry analysis identified seven StAR acetyl lysine residues under basal and in response to histone deacetylase (HDAC) inhibition. A number of HDAC inhibitors were capable of diminishing StAR expression and E2 synthesis in MCF7 cells. The validity of StAR protein acetylation and its correlation to HDAC inhibition mediated steroid synthesis was demonstrated in adrenocortical tumor H295R cells. These findings provide novel insights that StAR protein is abundantly expressed in the most prevalent hormone sensitive breast cancer subtype, wherein inhibition of HDACs altered StAR acetylation patterns and decreased E2 levels, which may have important therapeutic implications in the prevention and treatment of this devastating disease.

KEYWORDS:

Acetylation; Breast cancer; Estrogen; HDAC inhibition; StAR; Steroid biosynthesis

PMID:
30595381
DOI:
10.1016/j.bbrc.2018.12.145

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center