Department of Biochemistry and Molecular Biology, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, China.
J Endocrinol Invest. 2013 Oct;36(9):745-52. doi: 10.3275/8935. Epub 2013 Apr 12.
The processing of proprotein convertase (PC)-mediated neuropeptide plays a very important role in carcinogenesis and tumor proliferation.
To investigate proneuropeptide processing mechanism in tumorigenesis and tumor proliferation.
The expression and processing profiles of PC1, carboxypeptidase E (CPE), PC2, GHRH, or neuropeptide Y (NPY) gene and protein level were investigated between 42 human breast tumor tissues and 21 tumor-adjacent normal tissues.
Gene analyses indicated that the proPC1, CPE, or preproNPY gene had higher expression in the breast tumor tissues, whereas the proPC2 or preproGHRH gene showed lower expression in the tissues. Protein analyses showed that the proPC1, PC1, CPE, GHRH, and preproNPY proteins were upregulated in the tumor tissues, whereas the proPC2, PC2, preproGHRH, and NPY proteins were down-regulated in them. The tissue results were highly corroborated with the serum data from the tumor patients and healthy women.
The higher PC1 and CPE expressions as well as the transformation of more proGHRH into active GHRH peptide suggest stronger PC1/CPE-mediated neuropeptide processing in the tumor, whereas the lower PC2 expression as well as the transformation of less proNPY into active NPY peptide suggests a weak PC2-mediated processing in it. The alterations of the convertase expressions and processing show that there is a differential proprotein processing system in the tumor, which leads to the abnormal distributions of species, ratio, and concentration of (pro)peptide(s) in the microenvironment of cells. The latter may contribute to cancer progression.
蛋白原转化酶（PC）介导的神经肽加工在致癌作用和肿瘤增殖中起着非常重要的作用。
研究肿瘤发生和肿瘤增殖中前神经肽加工的机制。
在 42 个人类乳腺肿瘤组织和 21 个肿瘤邻近正常组织之间，研究了 PC1、羧肽酶 E（CPE）、PC2、GHRH 或神经肽 Y（NPY）基因和蛋白水平的表达和加工谱。
基因分析表明，前 PC1、CPE 或前 NPY 基因在乳腺肿瘤组织中表达较高，而前 PC2 或前 GHRH 基因在组织中表达较低。蛋白分析表明，前 PC1、PC1、CPE、GHRH 和前 NPY 蛋白在肿瘤组织中上调，而前 PC2、PC2、前 GHRH 和 NPY 蛋白在其中下调。组织结果与肿瘤患者和健康女性的血清数据高度吻合。
较高的 PC1 和 CPE 表达以及更多的前 GHRH 转化为活性 GHRH 肽表明肿瘤中 PC1/CPE 介导的神经肽加工更强，而较低的 PC2 表达以及更少的前 NPY 转化为活性 NPY 肽表明其较弱的 PC2 介导的加工。转换酶表达和加工的改变表明肿瘤中存在差异的蛋白原加工系统，导致细胞微环境中（前）肽的种类、比例和浓度的异常分布。后者可能导致癌症进展。
