VPRBP 蛋白与Abl 激酶诱发、抑制前列腺癌的 一种物理机制

在本文基于Hill动力学与Michaelis-Menten方程，建立理论模型研究VPRBP蛋白与Abl激酶诱发、抑制前列腺癌的一种物理机制.研究发现，DNA损伤使得ATM(共济失调毛细血管扩张症突变)很快激活，并激活上调p53蛋白表达，DNA损伤的后续破坏会在很大程度上通过p53表达上调而被抑制. VPRBP通过上调MDM2蛋白的激活水平，使得p53表达水平异常，进而无法正常抑制前列腺癌的发生发展.通过考察Abl在前列腺癌进程中的作用发现，Abl使得AKT的表达水平下调，由于Abl对AKT的抑制作用，致使在AKT信号通路中MDM2表达水平受到抑制，进而稳定p53表达.由此表明了，过少的Abl对AKT的抑制程度减弱，不仅使得细胞代谢出现紊乱，而且还会促使p53正常的周期表达水平异常，对DNA损伤诱发的肿瘤抑制性减弱，进而促进前列腺癌的发生发展.基于本文模型，可以预测VPRBP与Abl作为诱发、抑制前列腺癌的调节剂对现有和潜在的抗癌治疗较为敏感. VPRBP与Abl在诱发、抑制前列腺癌过程中的时滞效应，导致信号通路中p53与PTEN蓄积量增多、AKT蓄积量减少，以及Plk1周期振荡相位转移...

A physical mechanism of VPRBP protein and Abl kinase inducing and inhibiting prostate cancer

In this paper, based on Hill dynamics and Michaelis-Menten equation, we built a theoretical model to study a physical mechanism of VPRBP protein and Abl kinase inducing and inhibiting prostate cancer. We found that DNA damage quickly activates ATM and activates the up-regulation of p53. The subsequent damage of DNA damage will be largely inhibited by the up-regulation of p53 expression. VPRBP protein up-regulates MDM2, which makes the expression level of p53 abnormal. Thus, it is impossible to normalize the occurrence and development of prostate cancer. By investigating the role of Abl in the progression of prostate cancer, We also found that Ab1 down-regulates the expression level of AKT. Due to the inhibitory effect of Ab1 on AKT, which inhibits the expression level of MDM2 in the AKT signaling pathway, thereby stabilizing the expression of p53. This indicates that the deficient Ab1 can weaken the degree of inhibition of AKT. It not only makes cell metabolism disorder, but also promote the abnormal expression level of p53 in the normal cycle, and weaken the tumor suppression induced by DNA damage, which promote the occurrence and development of prostate cancer. Based on the model in this paper, it can be predicted that VPRBP and Abl as regulators that induce and inhibit prostate cancer are more sensitive to existing and potential anti-cancer treatments. VPRBP and Abl act as a time delay effect in the process of inducing and inhibiting prostate cancer, which result in increased accumulation of p53 and PTEN in the signal pathway, and decreased AKT, as well as Plk1 phase shift of periodic oscillations. It can used to predict the cell cycle process aimed at blocking prostate cancer cells potential therapeutic effect. The results of this paper reveal a regulatory mechanism of VPRBP protein and Abl in the process of inducing and inhibiting prostate cancer. The theoretical results are consistent with experiments and can provide a theoretical basis for the design of treatment plans that block prostate cancer.