Abstract
Tip60, an oncogene, accelerates cell growth by regulating androgen receptor translocation into the nucleus in prostate cancer. However, the mechanism of Tip60 in the response of prostate cancer to radiotherapy, and radioresistance, has not been studied. Using human prostate cancer samples and two human prostate cancer cell lines (LNCaP and DU145), Tip60 protein expression and the acetylation of ataxia telangiectasia mutant (ATM) were analysed by western blotting and immunoprecipitation. Tip60 was downregulated with small interfering RNA. Cells were irradiated using X‐rays at 0.25 Gy·min−1. Cell viability was assessed by the MTT assay. The expression of Tip60 protein was increased in radioresistant prostate cancer tissues in comparison with radiosensitive tissues, which was also confirmed in both irradiated DU145 and LNCaP cells. Furthermore, the acetylation of ATM was also upregulated in a time‐dependent manner after irradiation of both DU145 and LNCaP cells. Additionally, depletion of Tip60 decreased the survival of LNCaP and DU145 cells by inducing apoptosis, reduced the acetylation of ATM and decreased the expression of phosphorylated ATM, Chk2 and cdc25A in both DU145 and LNCaP cells after X‐ray irradiation. The results of this study demonstrated that the expression of Tip60 may be related to the radioresistance of prostate cancer and could serve as a promising predictive factor for prostate cancer patients receiving radiotherapy.
Highlights
IntroductionThe mechanism of Tip in the response of prostate cancer to radiotherapy, and radioresistance, has not been studied
The results of this study demonstrated that the expression of Tip60 may be related to the radioresistance of prostate cancer and could serve as a promising predictive factor for prostate cancer patients receiving radiotherapy
Tip60 expression was significantly higher in the radioresistant than radiosensitive prostate cancer tissues (Fig. 1). This indicated that Tip60 may be closely associated with postoperative radiotherapy resistance of prostate cancer
Summary
The mechanism of Tip in the response of prostate cancer to radiotherapy, and radioresistance, has not been studied. Using human prostate cancer samples and two human prostate cancer cell lines (LNCaP and DU145), Tip protein expression and the acetylation of ataxia telangiectasia mutant (ATM) were analysed by western blotting and immunoprecipitation. The expression of Tip protein was increased in radioresistant prostate cancer tissues in comparison with radiosensitive tissues, which was confirmed in both irradiated DU145 and LNCaP cells. The 5-year survival from prostate cancer has strikingly increased with the development of new treatment methods, it remains one of the leading causes of cancer death in men worldwide [4]. Relapse is found in approximately 10–70% of prostate cancer patients treated with radiotherapy, indicating that some cancer cells may be resistant to this treatment [5,6]. Lysine acetyltransferase 5, known as Tip, was first reported by Kamine et al [8] as a cofactor of Tat, Abbreviations AR, androgen receptor; ATM, ataxia telangiectasia mutant; HATs, histone acetyltransferases; siRNA, lentivirus-mediated small interfering RNA
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call