title: Rb deficiency accelerates progression of carcinoma of the urinary bladder in vivo and in vitro through inhibiting autophagy and apoptosis.
abstract: Urinary bladder cancer is known as a common cancer diagnosed across the world and results in significant mortality and morbidity rates among patients. The retinoblastoma (Rb) protein, as a main tumor suppressor, controls cellular responses to potentially oncogenic stimulation. Rb phosphorylation could disrupt E2F complex formation, resulting in diverse transcription factor dysfunction. In our study, we investigated how Rb is involved in controlling urinary bladder cancer progression. The results indicate that Rb expression is reduced in mice with urinary bladder tumor, and its suppression leads to urinary bladder cancer progression in vivo and in vitro. Rb mutation directly results in tumor size with lower survival rate in vivo. Rb knockdown in vitro promoted bladder tumor cell proliferation, migration and invasion. Interestingly, Rb knockout and knockdown result in autophagy and apoptosis inhibition via suppressing p53 and caspase-3 signaling pathways, enhancing bladder cancer development in vitro and in vivo. These findings reveal that Rb deficiency accelerated urinary bladder cancer progression, exposing an important role of Rb in suppressing urinary bladder cancer for treatment in the future.
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: 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: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics*; D015398:Signal Transduction; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001743:Urinary Bladder; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3