Skip to Content
Merck
  • An Epigenetic Reprogramming Strategy to Resensitize Radioresistant Prostate Cancer Cells.

An Epigenetic Reprogramming Strategy to Resensitize Radioresistant Prostate Cancer Cells.

Cancer research (2016-03-18)
Claudia Peitzsch, Monica Cojoc, Linda Hein, Ina Kurth, Katrin Mäbert, Franziska Trautmann, Barbara Klink, Evelin Schröck, Manfred P Wirth, Mechthild Krause, Eduard A Stakhovsky, Gennady D Telegeev, Vladimir Novotny, Marieta Toma, Michael Muders, Gustavo B Baretton, Fiona M Frame, Norman J Maitland, Michael Baumann, Anna Dubrovska
ABSTRACT

Radiotherapy is a mainstay of curative prostate cancer treatment, but risks of recurrence after treatment remain significant in locally advanced disease. Given that tumor relapse can be attributed to a population of cancer stem cells (CSC) that survives radiotherapy, analysis of this cell population might illuminate tactics to personalize treatment. However, this direction remains challenging given the plastic nature of prostate cancers following treatment. We show here that irradiating prostate cancer cells stimulates a durable upregulation of stem cell markers that epigenetically reprogram these cells. In both tumorigenic and radioresistant cell populations, a phenotypic switch occurred during a course of radiotherapy that was associated with stable genetic and epigenetic changes. Specifically, we found that irradiation triggered histone H3 methylation at the promoter of the CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), stimulating its gene transcription. Inhibiting this methylation event triggered apoptosis, promoted radiosensitization, and hindered tumorigenicity of radioresistant prostate cancer cells. Overall, our results suggest that epigenetic therapies may restore the cytotoxic effects of irradiation in radioresistant CSC populations. Cancer Res; 76(9); 2637-51. ©2016 AACR.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-ALDH1A3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-IGF-IR Antibody, clone JBW902, clone JBW902, Upstate®, from mouse
Sigma-Aldrich
Chromatin Immunoprecipitation (ChIP) Assay Kit, Contains all necessary reagents to perform 22 individual chromatin immunoprecipitation (ChIP) reactions using inexpensive protein A agarose beads.