and mutations as drivers of paclitaxel resistance in breast cancer cells.

Breast cancer (BC) is the most prevalent cancer type in the world, with increasing incidence rates. Drug resistance is a notable factor that limits the effectiveness of BC therapy. Paclitaxel (PTX), a chemotherapeutic agent belonging to the taxane class, is commonly used in BC; however, its efficacy is often compromised by drug resistance, which is primarily attributed to genetic alterations. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and wingless-type MMTV integration site family/β-catenin signaling pathways are involved in essential cellular processes, such as proliferation, apoptosis and maintenance of homeostasis. Dysregulated activation of these pathways is strongly associated with carcinogenesis and drug resistance. In the present study, the potential effects of (E17K/E49K/L52R) and catenin β-1 (; S33P/T41A/S45F) mutations on PTX resistance in BC were investigated using site-directed mutagenesis, transient transfection, MTS assay and western blot analyses. The results of the present study indicated that -E17K/E49K and -S45F/T41A mutations induced PTX resistance compared with -wild-type (WT) and -WT in MCF-7 cells, respectively. In MDA-MB-231 cells, all three mutations (E17K/E49K/L52R) triggered PTX resistance compared with -WT, while none of the mutations exhibited such an effect. In conclusion, mutations may serve as a biomarker for PTX resistance in both estrogen receptor (ER)(+)/progesterone receptor (PR)(+)/HER2(-) and triple negative BC, while mutations may be a potential biomarker for PTX resistance in ER(+)/PR(+)/HER2(-) BC.