Upregulation and activation of δ­opioid receptors promotes the progression of human breast cancer.

ABSTRACT

δ­opioid receptor (DOR) belongs to the family of G protein­coupled 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 concentration­dependent 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 signal­regulated 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.