title: Rb knockdown accelerates bladder cancer progression through E2F3 activation.
abstract: Bladder cancer is one of the most common cancers diagnosed in the world and leads to significant mortality and morbidity among affected patients. The retinoblastoma (Rb) protein is a main tumor suppressor, controlling cellular responses to potentially oncogenic stimulation. E2F3 was invariably disrupted in different human cancers for its central role in the control of cellular proliferation. Here, we investigated how Rb is integrated to control bladder cancer progression through E2F3 and p53 regulation. The results exhibit that Rb expression is lower in patients with bladder tumor, while E2F3 level is high. Rb knockdown enhanced bladder tumor cell proliferation and migration, aggravated with p53 silence. Interestingly, Rb silence results in E2F3, Myc and mTOR signaling pathway activation, contributing to bladder cancer cell proliferation and apoptosis suppression mainly through caspase-3 inhibition in vitro and in vivo. Immunohistochemical analysis revealed that Rb is highly expressed in normal bladder cells, but was repressed in tumor tissues of the bladder completely, suggesting a possible role of Rb as a tumor suppressor.
authors.affiliation: Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Jiang-Ping
authors.initials: JP
authors.lastname: Wang
authors.affiliation: Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Xu
authors.affiliation: Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D050699:E2F3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D053148:Caspase 3