title: AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation.
abstract: Metabolomic research has revealed that metabolites play an important role in prostate cancer development and progression. Previous studies have suggested that prostate cancer cell proliferation is induced by advanced glycation end products (AGEs) exposure, but the mechanism of this induction remains unknown. This study investigated the molecular mechanisms underlying the proliferative response of prostate cancer cell to the interaction of AGEs and the receptor for advanced glycation end products (RAGE). To investigate this mechanism, we used Western blotting to evaluate the responses of the retinoblastoma (Rb), p-Rb and PI3K/Akt pathway to AGEs stimulation. We also examined the effect of knocking down Rb and blocking the PI3K/Akt pathway on AGEs induced PC-3 cell proliferation. Our results indicated that AGE-RAGE interaction enhanced Rb phosphorylation and subsequently decreased total Rb levels. Bioinformatics analysis further indicated a negative correlation between RAGE and RB1 expression in prostate cancer tissue. Furthermore, we observed that AGEs stimulation activated the PI3K/Akt signaling pathway and that blocking PI3K/Akt signaling abrogated AGEs-induced cell proliferation. We report, for the first time, that AGE-RAGE interaction enhances prostate cancer cell proliferation by phosphorylation of Rb via the PI3K/Akt signaling pathway.
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University Guangzhou 510515, China ; Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University Guangzhou 510515, China.
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Bao
authors.affiliation: Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University Guangzhou 510515, China.
authors.forename: Min-Yi
authors.initials: MY
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Nanfang Hospital, Southern Medical University Guangzhou 510515, China.
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Molecular Oncology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London London, UK.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Affiliated Chaozhou Central Hospital of Southern Medical University Chaozhou 521021, China.
authors.forename: Ying-Qia
authors.initials: YQ
authors.lastname: Hong
authors.affiliation: Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University Guangzhou 510515, China.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Luo
authors.affiliation: Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University Guangzhou 510515, China.
authors.forename: Zhong-Lu
authors.initials: ZL
authors.lastname: Ren
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University Guangzhou 510515, China.
authors.forename: Shan-Chao
authors.initials: SC
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University Guangzhou 510515, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
keywords: AGEs; Akt; RAGE; proliferation; prostate cancer; retinoblastoma