<em>AKT1</em> and <em>CTNNB1</em> mutations as drivers of paclitaxel resistance in breast cancer cells

Altiparmak-Ulbegi,Gulsum; Hasbal-Celikok,Gozde; Aksoy-Sagirli,Pinar

doi:10.3892/ol.2025.15070

AKT1 and CTNNB1 mutations as drivers of paclitaxel resistance in breast cancer cells

Authors:
- Gulsum Altiparmak-Ulbegi
- Gozde Hasbal-Celikok
- Pinar Aksoy-Sagirli
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Affiliations: Department of Biochemistry, Faculty of Pharmacy, Istanbul University, 34116 Istanbul, Türkiye
Published online on: May 2, 2025 https://doi.org/10.3892/ol.2025.15070
Article Number: 324

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Abstract

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 AKT1 (E17K/E49K/L52R) and catenin β‑1 (CTNNB1; S33P/T41A/S45F) mutations on PTX resistance in BC were investigated in vitro using site‑directed mutagenesis, transient transfection, MTS assay and western blot analyses. The results of the present study indicated that AKT1‑E17K/E49K and CTNNB1‑S45F/T41A mutations induced PTX resistance compared with AKT1‑wild‑type (WT) and CTNNB1‑WT in MCF‑7 cells, respectively. In MDA‑MB‑231 cells, all three AKT1 mutations (E17K/E49K/L52R) triggered PTX resistance compared with AKT1‑WT, while none of the CTNNB1 mutations exhibited such an effect. In conclusion, AKT1 mutations may serve as a biomarker for PTX resistance in both estrogen receptor (ER)(+)/progesterone receptor (PR)(+)/HER2(‑) and triple negative BC, while CTNNB1 mutations may be a potential biomarker for PTX resistance in ER(+)/PR(+)/HER2(‑) BC.

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