Full Text:   <945>

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CLC number: R737.9

On-line Access: 2017-04-05

Received: 2016-04-24

Revision Accepted: 2016-08-17

Crosschecked: 2017-03-13

Cited: 0

Clicked: 1779

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Shi-chong Liao

http://orcid.org/0000-0002-3964-5469

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.4 P.334-342

10.1631/jzus.B1600184


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


Author(s):  Shi-chong Liao, Jin-xin Li, Li Yu, Sheng-rong Sun

Affiliation(s):  Department of Thyroid and Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; more

Corresponding email(s):   sun137@sina.com

Key Words:  Protein tyrosine phosphatase 1B (PTP1B), Signal transduction and activator of transcription 3 (STAT3), Breast cancer, Tumorigenesis


Shi-chong Liao, Jin-xin Li, Li Yu, Sheng-rong Sun. Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer[J]. Journal of Zhejiang University Science B, 2017, 18(4): 334-342.

@article{title="Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer",
author="Shi-chong Liao, Jin-xin Li, Li Yu, Sheng-rong Sun",
journal="Journal of Zhejiang University Science B",
volume="18",
number="4",
pages="334-342",
year="2017",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600184"
}

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%T Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer
%A Shi-chong Liao
%A Jin-xin Li
%A Li Yu
%A Sheng-rong Sun
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%DOI 10.1631/jzus.B1600184

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T1 - Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer
A1 - Shi-chong Liao
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VL - 18
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1600184


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.

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。

关键词:蛋白酪氨酸磷酸酶1B(PTP1B);信号转导与转录激活因子3(STAT3);乳腺癌;肿瘤发生

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]ACS (American Cancer Society), 2010. Breast Cancer Facts & Figures 2009–2010. American Cancer Society, Atlanta, p.28.

[2]Arias-Romero, L.E., Saha, S., Villamar-Cruz, O., et al., 2009. Activation of Src by protein tyrosine phosphatase 1B is required for ErbB2 transformation of human breast epithelial cells. Cancer Res., 69(11):4582-4588.

[3]Baselga, J., Norton, L., 2002. Focus on breast cancer. Cancer Cell, 1(4):319-322.

[4]Bence, K.K., Delibegovic, M., Xue, B., et al., 2006. Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat. Med., 12(8):917-924.

[5]Bentires-Alj, M., Neel, B.G., 2007. Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Cancer Res., 67(6):2420-2424.

[6]Bjorge, J.D., Pang, A., Fujita, D.J., 2000. Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J. Biol. Chem., 275(52):41439-41446.

[7]Boute, N., Boubekeur, S., Lacasa, D., et al., 2003. Dynamics of the interaction between the insulin receptor and protein tyrosine-phosphatase 1B in living cells. EMBO Rep., 4(3):313-319.

[8]Buffart, T.E., van Grieken, N.C., Tijssen, M., et al., 2009. High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers. Virchows Arch., 455(3):213-223.

[9]Dubé, N., Tremblay, M.L., 2004. Beyond the metabolic function of PTP1B. Cell Cycle, 3(5):548-551.

[10]Dubé, N., Cheng, A., Tremblay, M.L., 2004. The role of protein tyrosine phosphatase 1B in Ras signaling. Proc. Natl. Acad. Sci. USA, 101(7):1834-1839.

[11]Dubé, N., Bourdeau, A., Heinonen, K.M., et al., 2005. Genetic ablation of protein tyrosine phosphatase 1B accelerates lymphomagenesis of p53-null mice through the regulation of B-cell development. Cancer Res., 65(21):10088-10095.

[12]Fischer, E.H., Charbonneau, H., Tonks, N.K., 1991. Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes. Science, 253(5018):401-406.

[13]Julien, S.G., Dubé, N., Read, M., et al., 2007. Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat. Genet., 39(3):338-346.

[14]Karnoub, A.E., Dash, A.B., Vo, A.P., et al., 2007. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 449(7162):557-563.

[15]Klaman, L.D., Boss, O., Peroni, O.D., et al., 2000. Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol. Cell. Biol., 20(15):5479-5489.

[16]LaMontagne, K.R.Jr., Hannon, G., Tonks, N.K., 1998. Protein tyrosine phosphatase PTP1B suppresses p210 bcr-abl-induced transformation of Rat-1 fibroblasts and promotes differentiation of K562 cells. Proc. Natl. Acad. Sci. USA, 95(24):14094-14099.

[17]Liu, F., Sells, M.A., Chernoff, J., 1998. Transformation suppression by protein tyrosine phosphatase 1B requires a functional SH3 ligand. Mol. Cell. Biol., 18(1):250-259.

[18]Mustelin, T., Feng, G.S., Bottini, N., et al., 2002. Protein tyrosine phosphatases. Front Biosci., 7:d85-d142.

[19]Nanney, L.B., Davidson, M.K., Gates, R.E., et al., 1997. Altered distribution and expression of protein tyrosine phosphatases in normal human skin as compared to squamous cell carcinomas. J. Cutan. Pathol., 24(9):521-532.

[20]Pinilla, S., Alt, E., Abdul Khalek, F.J., et al., 2009. Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett., 284(1):80-85.

[21]Scotto, L., Narayan, G., Nandula, S.V., et al., 2008. Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Genes Chromosomes Cancer, 47(9):755-765.

[22]Wang, J., Liu, B., Chen, X., et al., 2012. PTP1B expression contributes to gastric cancer progression. Med. Oncol., 29(2):948-956.

[23]Warabi, M., Nemoto, T., Ohashi, K., et al., 2000. Expression of protein tyrosine phosphatases and its significance in esophageal cancer. Exp. Mol. Pathol., 68(3):187-195.

[24]Woodford-Thomas, T.A., Rhodes, J.D., Dixon, J.E., 1992. Expression of a protein tyrosine phosphatase in normal and v-src-transformed mouse 3T3 fibroblasts. J. Cell Biol., 117(2):401-414.

[25]Yang, J., Stark, G.R., 2008. Roles of unphosphorylated STATs in signaling. Cell Res., 18(4):443-451.

[26]Yang, J., Chatterjee-Kishore, M., Staugaitis, S.M., et al., 2005. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res., 65(3):939-947.

[27]Yang, J., Liao, X., Agarwal, M.K., et al., 2007. Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFκB. Genes Dev., 21(11):1396-1408.

[28]Zhang, Y., Yao, F., Yao, X., et al., 2009. Role of CCL5 in invasion, proliferation and proportion of CD44+/CD24 phenotype of MCF-7 cells and correlation of CCL5 and CCR5 expression with breast cancer progression. Oncol. Rep., 21(4):1113-1121.

[29]Zhang, Y., Liao, S., Fan, W., et al., 2014. Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells. Oncol. Rep., 32(6):2769-2776.

[30]Zhu, S., Bjorge, J.D., Fujita, D.J., 2007. PTP1B contributes to the oncogenic properties of colon cancer cells through Src activation. Cancer Res., 67(21):10129-10137.

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