BMP1 Appears to be Involved in GPER1-mediated Progression and Tamoxifen Resistance of Luminal A Breast Cancer Cells.

BACKGROUND/AIM: Bone morphogenetic protein 1 (BMP1) plays a role in the activation of both transforming growth factor-β (TGFβ) and BMP signaling pathways. We investigated whether BMP1 is involved in G-protein coupled estrogen receptor 1 (GPER1)-regulated progression of luminal A-type breast cancer cells.

MATERIALS AND

METHODS

Publicly available transcriptomic data from MCF7 breast cancer cells treated with the selective GPER1 agonist G1 were analyzed and the results, in particular the altered BMP1 expression, were validated by qPCR. Signs of epithelial-mesenchymal transition (EMT) were visualized by immune cytology. Invasion was quantified by modified Boyden chamber assay. Tamoxifen-resistant sublines of the MCF7 and T47D cell lines were established.

RESULTS

Activation of GPER1 by the agonist G1 increased the expression of BMP1 in MCF7 and T47D luminal A breast cancer cells. In addition, EMT and invasion was enhanced after GPER1 activation. This effect could be prevented in part by the BMP1 inhibitor UK383367. Tamoxifen-resistant MCF7-TR and T47D-TR cells exhibited higher BMP1 expression, signs of EMT and enhanced invasiveness compared to their tamoxifen-sensitive wild type. Blocking GPER1 in MCF7-TR and T47D-TR cells using the antagonist G36 led to reduction in BMP1 expression, a slight decrease in EMT, reduced cell invasion, and increased sensitivity to tamoxifen.

CONCLUSION

BMP1 appears to be involved in GPER1-mediated progression of luminal A breast cancer cells. In addition, BMP1 may play a role in tamoxifen-resistance.