Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53.
The androgen receptor (AR) and its coregulators have important roles in the carcinogenesis of prostate cancer. p53 is an important tumour suppressor gene, and the absence of a fundamental p53 response may predispose to cancer. Transgelin, known as an ARA54-associated AR inhibitor, can suppress AR function in LNCaP cells. In addition to these effects, we aimed to elucidate the proapoptotic effects of the protein on LNCaP and its underlying mechanisms, especially the interaction between transgelin and p53. Cell counting, flow cytometric analysis and terminal deoxynucleotidyl transferase-dUTP nick-end labelling assays were applied to measure the proapoptotic effect of transgelin. Using western blotting of p53 and double immunofluorescence staining of p53 with transgelin, we show that transfection of transgelin results in increasing cytoplasmic translocation of p53 and upregulation of p53 expression. We also found an interaction between transgelin and p53 in vivo by mammalian two-hybrid and coimmunoprecipitation assays. The activation of the mitochondria-associated apoptosis pathway was observed in LNCaP cells after transfection with transgelin. These results are indicative of p53-mediated mitochondria-associated apoptotic effects of transgelin on LNCaP cells in addition to its known suppressive effects on the AR pathway.
Zhang
Zhe-Wei
ZW
Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yang
Zhi-Ming
ZM
Zheng
Yi-Chun
YC
Chen
Zhao-Dian
ZD
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008840:Microfilament Proteins / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D008840:Microfilament Proteins; D009124:Muscle Proteins; D016159:Tumor Suppressor Protein p53; C051615:transgelin