TP53 upregulates α‑smooth muscle actin expression in tamoxifen‑resistant breast cancer cells

Kim,Sangmin; You,Daeun; Jeong,Yisun; Yu,Jonghan; Kim,Seok   Won; Nam,Seok   Jin; Lee,Jeong   Eon

doi:10.3892/or.2018.6910

TP53 upregulates α‑smooth muscle actin expression in tamoxifen‑resistant breast cancer cells

Authors:
- Sangmin Kim
- Daeun You
- Yisun Jeong
- Jonghan Yu
- Seok Won Kim
- Seok Jin Nam
- Jeong Eon Lee
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Affiliations: Breast Cancer Center, Samsung Medical Center, Gangnam‑gu, Seoul 06351, Republic of Korea, Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Gangnam‑gu, Seoul 06351, Republic of Korea
Published online on: December 6, 2018 https://doi.org/10.3892/or.2018.6910
Pages: 1075-1082

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Abstract

In a previous study, we reported that α‑smooth muscle actin (α‑SMA), one of the mesenchymal marker proteins, is highly expressed in tamoxifen‑resistant breast cancer (TamR) cells. However, the exact mechanism of α‑SMA expression in TamR cells is not fully understood. Here, we investigated the effect of TP53 on α‑SMA expression in breast cancer cells. The levels of α‑SMA mRNA and protein expression were analyzed by real‑time PCR and western blotting, respectively. In estrogen receptor‑positive [ER(+)] breast cancer patients, aberrant α‑SMA expression was found to be associated with a poor prognosis. The level of α‑SMA expression was significantly increased in established TamR cells compared to tamoxifen‑sensitive (TamS) cells. To verify the regulatory mechanism of α‑SMA expression, we analyzed diverse kinase activities between TamS and TamR cells. The activity of TP53 was markedly increased in the TamR cells. When TamS cells were treated with TP53 activator, Nutlin3 (Nut3), α‑SMA expression was increased in the TamS cells. In addition, α‑SMA expression was significantly increased by TP53 overexpression in breast cancer cells. On the contrary, the basal level of α‑SMA expression was decreased by the TP53 inhibitor, pifithrin‑α (PFT‑α). Taken together, we demonstrated that α‑SMA expression is regulated by TP53 activity in TamR cells.

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