title: Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways.
abstract: Cisplatin is a widely used anti-cancer drug. The B-cell translocation gene 2 (BTG2) is involved in the cell cycle transition regulation. We evaluated the cisplatin effects on prostate cancer cell proliferation and the expressions of BTG2, p53, androgen receptor (AR) and prostate specific antigen (PSA) in prostate carcinoma, p53 wild-type LNCaP or p53-null PC-3, cells. Cisplatin treatments attenuated cell prostate cancer cell growth through inducing Go/G1 cell cycle arrest in lower concentration and apoptosis at higher dosage. Cisplatin treatments enhanced p53 and BTG2 expression, repressed AR and PSA expression, and blocked the activation of androgen on the PSA secretion in LNCaP cells. BTG2 knockdown in LNCaP cells attenuated cisplatin-mediated growth inhibition. Cisplatin enhanced BTG2 gene expression dependent on the DNA fragment located within -173 to -82 upstream of BTG2 translation initiation site in prostate cancer cells. Mutation of the p53 response element from GGGCAGAGCCC to GGGCACC or mutation of the NFκB response element from GGAAAGTCC to GGAAAGGAA by site-directed mutagenesis abolished the stimulation of cisplatin on the BTG2 promoter activity in LNCaP or PC-3 cells, respectively. Our results indicated that cisplatin attenuates prostate cancer cell proliferation partly mediated by upregulation of BTG2 through the p53-dependent pathway or p53-independent NFκB pathway.
authors: 1] Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC [2].
authors: Kun-Chun
authors: KC
authors: Chiang
authors: 1] Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan, ROC [2].
authors: Ke-Hung
authors: KH
authors: Tsui
authors: Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Li-Chuan
authors: LC
authors: Chung
authors: Department of General Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Chun-Nan
authors: CN
authors: Yeh
authors: School of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Tsui-Hsia
authors: TH
authors: Feng
authors: National Kaohsiung University of Hospitality and Tourism, Hsiao-Kang, Kaohsiung Taiwan R.O.C.
authors: Wen-Tsung
authors: WT
authors: Chen
authors: Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Phei-Lang
authors: PL
authors: Chang
authors: Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Hou-Yu
authors: HY
authors: Chiang
authors: Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Horng-Heng
authors: HH
authors: Juang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000097782:NF-kappaB-Inducing Kinase; C495901:TP53 protein, human; C070114:BTG2 protein, human