WNT signaling pathway regulator- affects oncogenesis and prognosis of basal-like breast cancer.

BACKGROUND

Breast cancer is the most common malignant cancer in women worldwide and is one of the leading causes of cancer death. Basal-like breast cancer (BLBC) is an aggressive subtype of breast cancer for which targeted therapy has poor efficacy. Therefore, research into the molecular pathogenesis of BLBC is urgent for developing effective targeted therapeutic treatments.

METHODS

We collected relevant data from the Cancer Genome Atlas (TCGA), including transcriptome, copy number variation, and survival data. We also gathered 30 pairs clinical samples of cancer tissues and non-cancerous tissues to perform Western Blotting (WB) to reveal the encoded protein expression levels. Besides, we knocked down frequently rearranged in advanced T-cell lymphomas 2 () expression in two representative cell lines (T47D and MDA-MB-231 cells). The cell cycle progression was analyzed, while the apoptosis experiments were also conducted to explore the molecular pathogenesis of in BLBC.

RESULTS

The aberrant activation of the WNT pathway and highly expressed were specifically identified across the BLBC genome comparing to other types of tumor. In addition, expression was found to be positively associated with its copy number variations (P=9.126×10). For further investigation, we found the expression level of FRAT2 was related to the poor overall survival of BLBC patients (P=0.049). The results of WB revealed that FRTA2-encoded protein was overexpressed in BLBC tissues. Based on results in T47D and MDA-MB-231 cells , we found that knocking down can inhibit the proliferation of these two cell lines. In cell cycle progression experiments, cell cycle arrested in the G2/M phase. Meanwhile, increased apoptosis was also found in the sh cell group .

CONCLUSIONS

In BLBC basal-like breast cancer, we can assume that is a potential treatment target.