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Tip60 is associated with resistance to X-ray irradiation in prostate cancer

Xin Xie1, Zhaoping Xu1, Chenghe Wang1

  • 1Department of Urology Ruijin Hospital Shanghai Jiaotong University, School of Medicine China.

FEBS Open Bio
|February 14, 2018
PubMed

Insights

Tip60 protein expression is elevated in radioresistant prostate cancer, suggesting it may predict treatment response. Lowering Tip60 levels increases cancer cell death after radiation therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Tip60 is an oncogene that promotes prostate cancer cell growth.
  • The role of Tip60 in prostate cancer radioresistance remains uninvestigated.

Purpose of the Study:

  • To investigate the mechanism of Tip60 in prostate cancer response to radiotherapy.
  • To determine if Tip60 expression correlates with radioresistance and can serve as a predictive factor.

Main Methods:

  • Analysis of Tip60 protein expression and ATM acetylation in human prostate cancer samples and cell lines (LNCaP, DU145) using western blotting and immunoprecipitation.
  • Tip60 downregulation via small interfering RNA.
  • X-ray irradiation of cells and assessment of cell viability (MTT assay).

Main Results:

  • Tip60 protein expression was higher in radioresistant prostate cancer tissues and irradiated cells compared to radiosensitive counterparts.
  • ATM acetylation and phosphorylation of ATM, Chk2, and cdc25A increased post-irradiation.
  • Tip60 depletion reduced cell survival, induced apoptosis, and decreased ATM acetylation and downstream signaling after irradiation.

Conclusions:

  • Tip60 expression is associated with prostate cancer radioresistance.
  • Tip60 may play a crucial role in DNA damage response following radiotherapy.
  • Tip60 could be a potential predictive biomarker for prostate cancer radiotherapy outcomes.
Keywords:
Tip60ataxia telangiectasia mutantprostate cancerradioresistance

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