ING3 promotes prostate cancer growth by activating the androgen receptor

BMC Medicine
Arash NabbiKarl Riabowol

Abstract

The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development. Biopsies of 265 patients with prostate cancer were stained for ING3, pan-cytokeratin, and DNA. LNCaP and C4-2 androgen-responsive cells were used for in vitro assays including immunoprecipitation, western blotting, Luciferase reporter assay and quantitative polymerase chain reaction. Cell viability and migration assays were performed in prostate cancer cell lines using scrambled siRNA or siRNA targeting ING3. We find that ING3 levels and AR activity positively correlate in prostate cancer. ING3 potentiates androgen effects, increasing expression of androgen-regulated genes and androgen response element-driven reporters to promote growth and anchorage-independent growth. Conversely, ING3 knockdown inhibits prostate cancer cell growth and invasion....Continue Reading

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Citations

Jan 31, 2018·British Journal of Cancer·Urszula L McClurgOlivier Binda
Feb 9, 2018·Endocrinology·Bharti Jaiswal, Ashish Gupta
Nov 23, 2019·Cancers·Arthur DantasKarl Riabowol
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May 8, 2021·Frontiers in Oncology·Chunhua LiuWeiwei Liu
May 1, 2021·Cancers·Karine Jacquet, Olivier Binda

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Methods Mentioned

BETA
acetylation
transfection
PCR
immunoprecipitation
ChIP
RNAseq
pull down
nuclear translocation
co-immunoprecipitations

Software Mentioned

ENCODE
ImageJ
SPSS
Graphpad Prism

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