Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer

Abstract

The protein tyrosine phosphatase 1B (PTP1B) is an important regulator of metabolism. The relationship between PTP1B and tumors is quite complex. The purpose of this study is to explore the expression pattern and role of PTP1B in breast cancer. The expression of PTP1B was detected in 67 samples of breast cancer tissue by Western blot. Cell growth assay, Transwell migration assay, and Scratch motility assay were used to examine the proliferation and migration of MCF-7 with and without PTP1B. The total levels and phosphorylated levels of signal transduction and activator of transcription 3 (STAT3) and the expression of C-C motif chemokine ligand 5 (CCL5) were also examined by Western blot. PTP1B was overexpressed in over 70% of breast cancer tissues, correlating with patients with estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-positive tumors. The data also showed that both tumor size and lymph node metastasis were significantly higher in patients with a higher level of PTP1B. The proliferation and migration of MCF-7 cells were found to be inhibited after knocking down the gene of PTP1B. Our data also showed that PTP1B could up-regulate the dephosphorylated level of STAT3, which could increase the expression of CCL5. These phenomena indicated that PTP1B may play a crucial role in the development of breast cancer.

中文概要

题目

蛋白酪氨酸磷酸酶1B 在乳腺癌进展中的作用

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。