CCAAT/Enhancer binding protein β controls androgen-deprivation-induced senescence in prostate cancer cells

Oncogene
D J BarakatI Paz-Priel

Abstract

The processes associated with transition to castration-resistant prostate cancer (PC) growth are not well understood. Cellular senescence is a stable cell cycle arrest that occurs in response to sublethal stress. It is often overcome in malignant transformation to confer a survival advantage. CCAAT/Enhancer Binding Protein (C/EBP) β function is frequently deregulated in human malignancies and interestingly, androgen-sensitive PC cells express primarily the liver-enriched inhibitory protein isoform. We found that C/EBPβ expression is negatively regulated by androgen receptor (AR) activity and that treatment of androgen-sensitive cell lines with anti-androgens increases C/EBPβ mRNA and protein levels. Accordingly, we also find that C/EBPβ levels are significantly elevated in primary PC samples from castration-resistant compared with therapy-naive patients. Chromatin immunoprecipitation demonstrated enhanced binding of the AR to the proximal promoter of the CEBPB gene in the presence of dihydroxytestosterone. Upon androgen deprivation, induction of C/EBPβ is facilitated by active transcription as evident by increased histone 3 acetylation at the C/EBPβ promoter. Also, the androgen agonist R1881 suppresses the activity of a CEBPB p...Continue Reading

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Citations

Apr 10, 2019·American Journal of Respiratory Cell and Molecular Biology·Shruthi HamsanathanAna L Mora
Apr 3, 2020·Cancers·Tareq SalehDavid A Gewirtz
Jul 14, 2019·Cancer Research·Hsi-Wen YehYuh-Shan Jou
Feb 14, 2021·Cancers·Valerie J CarpenterDavid A Gewirtz
Jul 21, 2021·Life Science Alliance·Husen M UmerClaes Wadelius

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Methods Mentioned

BETA
castration
immunoprecipitation
acetylation
flow cytometry
fluorescence microscopy
transfection
PCR

Software Mentioned

TAL Effector
Nucleotide Targeter
ImageJ
TreeStar
FloJo Cytometric Analytical
Ensembl

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