title: PTTG1, A novel androgen responsive gene is required for androgen-induced prostate cancer cell growth and invasion.
abstract: Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex. Bioinformatics analysis and experiments using PTTG1 promoter deletion mutants showed that the PTTG1 promoter contains a putative androgen response element (ARE), which localizes in the -851 to -836 region of the promoter. Androgen activated androgen receptor (AR) binding to this ARE was confirmed by Chromatin immunoprecipitation (ChIP) assay. Furthermore, Knockdown of PTTG1 expression using short hairpin RNA significantly reduced androgen-induced LNCaP cell growth and invasion. In addition, we showed PTTG1 is highly expressed in metastasis prostate cancer tissue. These results suggest that PTTG1 is a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis.
authors.affiliation: Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.affiliation: Biobank for Clinical Data and Samples in Pediatric, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034, China.
authors.forename: Shengquan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Niu
authors.affiliation: The Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034, China. Electronic address: xin-dianqi@163.com.
authors.forename: Dianqi
authors.initials: D
authors.lastname: Xin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D064249:Securin / Q000235:genetics* / Q000378:metabolism
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human
keywords: Androgen responsive gene; PTTG1; Prostate cancer