β2-AR /PCBP2相互作用在胰腺癌发生发展中的作用及机制

长期的生活压力和精神紧张是胰腺癌的重要危险因素，其可通过肾上腺素受体通路发挥促癌作用。课题组前期研究发现β2-肾上腺素受体（β2-AR）可结合胞浆中的多聚胞嘧啶结合蛋白2（PCBP2），而PCBP2能够调节癌基因c-myc和K-ras的表达及促进胰腺癌细胞增殖。基于此，课题组提出假说：精神因素可通过β2-AR介导的PCBP2通路促进胰腺癌发展。本课题拟首先在胰腺癌临床组织中阐明β2-AR和PCBP2的表达关系；进而分析β2-AR和PCBP2的相互作用对下游c-myc和K-ras表达的调节作用，并研究此作用机制对胰腺癌细胞增殖能力的影响；最后在裸鼠动物模型中验证慢性焦虑通过β2-AR/PCBP2通路对胰腺癌发展的作用。该课题研究有助于阐明精神因素对胰腺癌的作用机制，并且能为胰腺癌的防治提供新的理论依据。

Chronic life pressure and mental stress is one of the significant risk factors for pancreatic cancer. β2-adrenergic receptor (β2-AR) on the surface of cancer cells plays the vital role in the oncogenesis of psychological factors. Our previous studies identified that β2-AR could combined with Poly(rC) Binding Protein 2 (PCBP2). Furthermore, PCBP2 could regulate the expression of c-myc and K-ras, and enhance pancreatic cancer cell proliferation. Based on this, we propose the hypothesis that psychological stress promotes the progression of pancreatic cancer via β2-AR-induced activation of PCBP2. In this project, we will detect the expression of β2-AR and PCBP2 in pancreatic cancer tissue sections, and analyze the association of the protein expression and clinicopathological parameters. Furthermore, we will explore the impact of β2-AR/PCBP2 interaction on the regulation of the expression of c-myc and K-ras, and exam the mechanism of facilitating cell growth ability. Finally, we will construct a subcutaneous xenograft model of pancreatic cancer which was exposed to social stress, in order to validate the results as the former. The project will clarify the molecular mechanisms of the effect of mental factors on pancreatic cancer development, and provide a theoretical basis for new prevention and treatment of pancreatic cancer.