AB044. AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation
AB044. AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation
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DOI：
10.21037/tau.2016.s044
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发表时间：
2016-04
影响因子：
2
通讯作者：
Hong Y
中科院分区：
文献类型：
--
作者：
Bao J;Bao Y;Zhao S;He M;Luo H;Ren Z;Lv Y;Hong Y
代谢组学研究表明，代谢物在前列腺癌的发生和发展中起着重要作用。以往的研究表明晚期糖基化终产物（AGEs）可诱导前列腺癌细胞增殖，但其诱导机制尚不清楚。本研究旨在探讨晚期糖基化终末产物受体（receptor for advanced glycation end products，AGEs）与前列腺癌细胞增殖反应的分子机制。为了探讨这一机制，我们使用Western印迹法来评估视网膜母细胞瘤（Rb），p-Rb和PI 3 K/Akt通路对AGEs刺激的反应。我们还研究了敲低Rb和阻断PI 3 K/Akt通路对AGEs诱导的PC-3细胞增殖的影响。我们的研究结果表明，AGE-Rb相互作用增强Rb磷酸化，随后降低总Rb水平。生物信息学分析进一步表明，前列腺癌组织中RB 1和Rb 1的表达呈负相关。此外，我们观察到AGEs刺激激活了PI 3 K/Akt信号通路，阻断PI 3 K/Akt信号通路可抑制AGEs诱导的细胞增殖。我们报告，第一次，AGE-Rb相互作用增强前列腺癌细胞增殖通过磷酸化Rb通过PI 3 K/Akt信号通路。
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 aim to investigate 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.