The clock gene BHLHE40 and atypical CCNG2 control androgen-induced cellular senescence as a novel tumor suppressive pathway in prostate cancer.

ABSTRACT:

Background

The androgen receptor (AR) is a drug target used to inhibit AR and prostate cancer (PCa) growth. Surprisingly, treatment with supraphysiological androgen level (SAL), used in bipolar androgen therapy, inhibits growth of PCa suggesting a tumor-suppressive activity by SAL. SAL was shown to induce cellular senescence in PCa.

Methods

RNA-seq and transcriptome analysis, ChIP-seq, human 3D PCa spheroids, mouse xenografted castration-resistant PCa, knockdown and overexpression, Co-immunoprecipitation (Co-IP), translocation analysis, immune detection, qRT-PCR, protein-protein interaction modelling.

Results

Here, mice xenografts with castration-resistant PCa tumors show that SAL inhibits cancer growth in vivo suggesting that SAL activates a tumor-suppressive mechani

SUBMITTER: Heidari Horestani M 

PROVIDER: S-EPMC11188219 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature