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δ-阿片受体的上调和激活促进人类乳腺癌的进展。

Upregulation and activation of δ‑opioid receptors promotes the progression of human breast cancer.

作者信息

Wei Yang-Chao, Zhang Bin, Li Xuan, Liu Xiao-Meng, Zhang Jing, Lei Biao, Li Bo, Zhai Run, Chen Qian, Li Yang

机构信息

Department of Medical Oncology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.

Department of Breast and Thyroid Surgery, The First Hospital of Jining, Jining, Shandong 272011, P.R. China.

出版信息

Oncol Rep. 2016 Nov;36(5):2579-2586. doi: 10.3892/or.2016.5109. Epub 2016 Sep 19.

Abstract

δ‑opioid receptor (DOR) belongs to the family of G protein‑coupled receptors (GPCRs). Numerous studies have shown that DOR is widely distributed in human peripheral tissues and is closely related to the development and progression of certain malignant tumours. However, there is controversy in the literature regarding whether DOR has an impact on the development and progression of human breast cancer. The present study comprehensively elaborates on the biological functions of DOR by determining the distribution of DOR expression in breast cancer tissues and cells and by further verifying the effects of DOR on breast cancer progression. DOR was found to be highly expressed in human breast cancer tissues and cells. In addition, the high expression level of DOR positively correlated with tumour grade and clinical stage and negatively correlated with breast cancer metastasis and prognosis. Upregulating and activating DOR promoted the proliferation of human breast cancer cells in a concentration‑dependent manner within a specific concentration range, whereas downregulating or inhibiting DOR activation significantly suppressed cell proliferation. The majority of tumour cells were arrested in G1 phase, and some cells exhibited apoptosis. DOR upregulation and activation induced protein kinase C (PKC) activation, resulting in increased phosphorylation levels of extracellular signal‑regulated kinases (ERKs). After inhibition of the PKC/ERK signalling pathway, the effects of DOR on breast cancer were significantly attenuated in vivo and in vitro. In summary, DOR is highly expressed in breast cancer and is closely related to its progression. These results suggest that DOR may serve as a potential biomarker for the early diagnosis of breast cancer and may be a viable molecular target for therapeutic intervention.

摘要

δ阿片受体(DOR)属于G蛋白偶联受体(GPCR)家族。大量研究表明,DOR广泛分布于人体外周组织,且与某些恶性肿瘤的发生发展密切相关。然而,关于DOR是否对人类乳腺癌的发生发展有影响,文献中存在争议。本研究通过确定DOR在乳腺癌组织和细胞中的表达分布,并进一步验证DOR对乳腺癌进展的影响,全面阐述了DOR的生物学功能。研究发现,DOR在人类乳腺癌组织和细胞中高表达。此外,DOR的高表达水平与肿瘤分级和临床分期呈正相关,与乳腺癌转移和预后呈负相关。在特定浓度范围内,上调并激活DOR以浓度依赖性方式促进人类乳腺癌细胞的增殖,而下调或抑制DOR激活则显著抑制细胞增殖。大多数肿瘤细胞停滞在G1期,部分细胞出现凋亡。DOR上调和激活诱导蛋白激酶C(PKC)激活,导致细胞外信号调节激酶(ERK)磷酸化水平升高。抑制PKC/ERK信号通路后,DOR在体内和体外对乳腺癌的影响均显著减弱。综上所述,DOR在乳腺癌中高表达,且与其进展密切相关。这些结果表明,DOR可能作为乳腺癌早期诊断的潜在生物标志物,也可能是治疗干预的可行分子靶点。

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