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蛋白酪氨酸磷酸酶 κ(PTPRK)是乳腺癌细胞黏附和侵袭的负调控因子,与乳腺癌的不良预后相关。

Protein tyrosine phosphatase kappa (PTPRK) is a negative regulator of adhesion and invasion of breast cancer cells, and associates with poor prognosis of breast cancer.

机构信息

Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

出版信息

J Cancer Res Clin Oncol. 2013 Jul;139(7):1129-39. doi: 10.1007/s00432-013-1421-5. Epub 2013 Apr 4.

Abstract

PURPOSE

Receptor-like protein tyrosine phosphatase kappa (PTPRK) has been shown to exhibit homophilic binding. It is a putative tumour suppressor in primary central nervous system lymphomas and colorectal cancer. The present study investigated the expression of PTPRK in breast cancer and the biological impact of PTPRK on breast cancer cells.

METHODS

Expression of PTPRK protein and gene transcript was examined in a cohort of breast cancer patients. The association of PTPRK transcript level and pathological and clinical aspects was then analysed. Knockdown of PTPRK in breast cancer cells was performed using a specific anti-PTPRK transgene. The impact of PTPRK knockdown on breast cancer cells was investigated using in vitro cell function assays.

RESULTS

Lower levels of PTPRK transcripts were seen in the advanced breast cancer. The reduced PTPRK transcript levels were associated with poor prognosis of the disease. PTPRK transcript levels were decreased in the primary tumours of patients who died from breast cancer or had metastases. Patients with lower expression of PTPRK had shorter survival compared with those higher expression levels of PTPRK. Knockdown of PTPRK resulted in increased proliferation, adhesion, invasion, and migration of breast cancer cells in vitro.

CONCLUSIONS

Decreased expression of PTPRK in breast cancer is correlated with poor prognosis. PTPRK is a negative regulator of adhesion, invasion, migration, and proliferation of breast cancer cells. This suggests that PTPRK is a potential tumour suppressor in breast cancer.

摘要

目的

已证实受体样蛋白酪氨酸磷酸酯酶 kappa(PTPRK)具有同型结合能力。它是原发性中枢神经系统淋巴瘤和结直肠癌的潜在肿瘤抑制因子。本研究调查了 PTPRK 在乳腺癌中的表达情况,以及 PTPRK 对乳腺癌细胞的生物学影响。

方法

在一组乳腺癌患者中检测了 PTPRK 蛋白和基因转录本的表达情况。然后分析了 PTPRK 转录本水平与病理和临床特征的相关性。使用特异性抗 PTPRK 转基因对乳腺癌细胞进行 PTPRK 敲低。使用体外细胞功能测定法研究了 PTPRK 敲低对乳腺癌细胞的影响。

结果

晚期乳腺癌患者的 PTPRK 转录本水平较低。降低的 PTPRK 转录本水平与疾病的不良预后相关。死于乳腺癌或发生转移的患者的原发肿瘤中 PTPRK 转录本水平降低。与 PTPRK 高表达的患者相比,PTPRK 低表达的患者生存时间更短。PTPRK 敲低导致乳腺癌细胞在体外的增殖、黏附、侵袭和迁移增加。

结论

乳腺癌中 PTPRK 的表达降低与预后不良相关。PTPRK 是乳腺癌细胞黏附、侵袭、迁移和增殖的负调节剂。这表明 PTPRK 是乳腺癌中的潜在肿瘤抑制因子。

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