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目的:讨论蛋白酪氨酸磷酸酶1B(PTP1B)在乳腺癌中的表达模式,及其在肿瘤进展中所起的作用。创新点:首次证明了PTP1B能够增加非磷酸化信号转导与转录激活因子3(STAT3)的水平,而非磷酸化STAT3与核转录因子(NF-κB)形成新的转录因子介导C-C型趋化因子配体5(CCL5)的表达,从而促进肿瘤细胞增殖和迁移,导致肿瘤恶性程度增加。方法:收集67名乳腺癌患者的癌组织和癌旁组织标本,并记录患者临床病理学特征,使用蛋白质免疫印迹法(Western blot)检测乳腺癌组织及癌旁组织PTP1B含量;研究PTP1B水平与患者临床病理特征关系;制作PTP1B基因敲除MCF-7细胞系,分别使用细胞生长实验、Transwell细胞迁移实验和划痕活力实验检测基因敲出组与对照组细胞增殖及迁移能力,使用Western blot检测两组细胞中磷酸化与非磷酸化STAT3表达水平和CCL5表达水平。结论:大约70%乳腺癌患者高表达PTP1B,并且随着患者TNM分期增加,患者PTP1B表达水平不断增加,同时PTP1B高表达与ER-、PR-和HER2+相关(表1和2);与对照组相比,PTP1B基因敲除组中肿瘤细胞增殖及迁移能力明显下降(图2和3),同时PTP1B可以通过上调STAT3非磷酸化水平来提高CCL5的表达,从而加快乳腺癌发生及发展(图4)。总之,PTP1B对乳腺癌的发生起到至关重要的作用。
Objective: To discuss the expression pattern of protein tyrosine phosphatase 1B (PTP1B) in breast cancer and its role in tumor progression. Innovations: It was first demonstrated that PTP1B increases the level of non-phosphorylated signal transducer and activator of transcription 3 (STAT3), whereas non-phosphorylated STAT3 forms a novel transcription factor with nuclear transcription factor (NF-κB) Factor 5 (CCL5) expression, thereby promoting tumor cell proliferation and migration, leading to increased malignancy of the tumor. Methods: Sixty-six breast cancer samples were collected from patients with breast cancer and their clinicopathological features were recorded. The levels of PTP1B in breast cancer tissues and adjacent tissues were detected by Western blot. (PTP1B knockout) MCF-7 cell line was used to detect the proliferation and migration of gene knockout group and control group by using cell growth assay, Transwell cell migration assay and scratch activity assay respectively. Western blot was used to detect two Phosphorylated and non-phosphorylated STAT3 and CCL5 expression in group cells. CONCLUSIONS: PTP1B is highly expressed in approximately 70% of breast cancer patients and is associated with an increased expression of PTP1B in patients with an increased TNM stage, while PTP1B is highly associated with ER-, PR- and HER2 + (Table 1 and 2) Compared with the PTP1B knockout group of tumor cell proliferation and migration ability decreased significantly (Figure 2 and 3), while PTP1B by upregulation of non-phosphorylated STAT3 to improve CCL5 expression, thereby accelerating the occurrence and development of breast cancer (Figure 4 ). In conclusion, PTP1B plays a crucial role in the development of breast cancer.