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同源异型框蛋白在发育中具有非常重要的作用,而同源异型框蛋白的异常表达和很多人类疾病相关,其中就包括前列腺癌的发生发展。我们通过分析TCGA数据库中前列腺癌病人样本MSX1的表达量发现,在肿瘤样本中MSX1表达量显著高于非肿瘤样本。因此我们检测正常永生化前列腺基底细胞系WPMY-1、雄激素依赖的前列腺癌细胞系LNCa P、雄激素非依赖的前列腺癌细胞系PC-3中MSX1的表达量,发现在雄激素依赖的前列腺癌细胞系LNCa P中MSX1表达量最高。为了探究MSX1在前列腺癌细胞中的作用,我们选取MSX1表达量较低且不受雄激素调控的PC-3细胞作为研究对象。研究表明过表达MSX1可以显著促进PC-3细胞的增殖。我们通过免疫沉淀技术确定了MSX1与GRP78蛋白相互作用,而GRP78蛋白可以调控AKT、ERK1/2等细胞周期相关蛋白从而调控细胞周期等细胞进程。因此推测MSX1通过和GRP78相互作用从而促进前列腺癌细胞增殖。我们的研究为阐明MSX1在前列腺癌发生发展中作用机理提供了一定的理论参考依据。
Homeobox proteins play a very important role in the development. The abnormal expression of homeobox proteins is associated with many human diseases, including the development of prostate cancer. By analyzing the expression level of MSX1 in a sample of prostate cancer patients in the TCGA database, we found that MSX1 expression was significantly higher in tumor samples than in non-tumor samples. Therefore, we examined the expression levels of MSX1 in the normal immortalized prostatic basal cell line WPMY-1, the androgen-dependent prostate cancer cell line LNCa P, and the androgen-independent prostate cancer cell line PC-3 and found that in androgen-dependent prostate The highest expression level of MSX1 was found in the cancer cell line LNCa P. To explore the role of MSX1 in prostate cancer cells, we selected PC-3 cells with low expression levels of MSX1 and not regulated by androgen. Studies have shown that overexpression of MSX1 can significantly promote PC-3 cell proliferation. We identified the interaction between MSX1 and GRP78 proteins by immunoprecipitation, and GRP78 protein regulates the cell cycle-related proteins such as AKT and ERK1 / 2 to regulate cellular processes such as cell cycle. Therefore, it is speculated that MSX1 promotes the proliferation of prostate cancer cells by interacting with GRP78. Our study provides a theoretical basis for elucidating the mechanism of MSX1 in the development of prostate cancer.