PRRX1 drives tamoxifen therapy resistance through induction of epithelial-mesenchymal transition in MCF-7 breast cancer cells.

Purpose: Resistance to endocrine therapies is a major cause of disease relapse and mortality in estrogen receptor (ER)-positive breast cancers, which has been associated with tumor epithelial-mesenchymal transition (EMT). In this study, we investigated the contribution of the EMT-inducing factor paired related homeobox 1 (PRRX1) to tamoxifen (TAM) resistance acquired using ER-positive MCF-7 breast cancer cells.

Methods: PRRX1 was overexpressed in MCF-7 cells through transfection; cells transfected with a blank vector served as the control. The morphological changes and transfection efficiency were observed by inverted fluorescence microscopy. The expression of ER and EMT-related proteins and genes was evaluated by Western blot and real-time polymerase chain reaction analysis, respectively. Finally, we evaluated the EMT features of the breast cancer cells and their response to TAM treatment.

Results: The transfection efficiency was greater than 80%, and the expression level of PRRX1 protein was significantly higher after transfection, whereas the expression of ER protein was significantly lower after transfection. The overexpression of PRRX1 changed the morphology of breast cancer cells from a "paving stone" to a long spindle shape. The mRNA expression levels of and vimentin were significantly higher, whereas that of E-cadherin was significantly lower after transfection. The proliferative level of the breast cancer cells after transfection was significantly increased at 12, 24 and 48 h after treatment with TAM. At 24 h of TAM treatment, the half-maximal inhibitory concentration of the transfected cells was significantly higher than that before transfection. Moreover, the PRRX1-overexpressing MCF-7 breast cancer cells acquired an EMT phenotype and displayed decreased levels of ER targets to ultimately acquire resistance to TAM.

Conclusions: PRRX1 overexpression can induce EMT to promote resistance to TAM in MCF-7 breast cancer cells, partly by reducing ER expression. It is suggested that in clinical practice, PRRX1 gene expression detection can be performed in patients with hormone-receptor-positive breast cancer to guide our medication and prognosis.