G Protein-Coupled Estrogen Receptor Is a Critical Regulator in Metastasis of Breast Cancer Cells

摘要

Estrogen signaling via GPER in breast cancers has been intensively discussed over years, but the underlying molecular mechanism remains to be fully elucidated, especially for the transcriptional profiles of the GPER under estrogen stimulation. In this study, we evaluated the potential role GPER in regulating invasion of metastatic breast cancer cell line MDA-MB-231 via transcriptional way. First, with primary breast cancer tissue samples, we found that the expression of GPER significantly coordinated with another membrane receptor-CXCR1. Besides, the expression level of these two proteins was associated with the development of the primary breast cancers. Second, to dissect the cross talk between GPER and CXCR1, we further our studies to detect the activation of ERK, Akt and transcriptional factor NF-kB. We found that upon estrogen stimulation, the phosphorylation level of ERK and Akt were rapidly increased and then resulted in the activation and nucleus translocation of NF-kB. When we considered the sub-sequence of the NF-kB activation, we found the autocrine of IL-8 was boosted by stimulation of the estrogen and followed by the promoted invasion of the MDA-MB-231 cells. In conclusion, our data demonstrated the estrogen-mediated GPER stimulation would regulate the invasive activities of metastatic breast cancer cell line MDA-MB-231 coupled with another membrane receptor CXCR1 via transcriptional pathway, the cross talk between GPER and CXCR1 may be another target for breast cancer therapies.