Characteristics of sphingomyelin metabolism in the MCF7 and BT474 radiotherapy‑resistant HER2‑positive breast cancer cell lines

Kikuchi,Megumi; Monzen,Satoru; Horikoshi,Mai; Tsuda,Shuri; Tatara,Yota; Wojcik,Andrzej; Mariya,Yasushi

doi:10.3892/ol.2024.14604

Characteristics of sphingomyelin metabolism in the MCF7 and BT474 radiotherapy‑resistant HER2‑positive breast cancer cell lines

Authors:
- Megumi Kikuchi
- Satoru Monzen
- Mai Horikoshi
- Shuri Tsuda
- Yota Tatara
- Andrzej Wojcik
- Yasushi Mariya
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Affiliations: Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan, Department of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan, Department of Molecular Biosciences, The Wenner‑Gren Institute, Stockholm University, Stockholm, Stockholm SE‑10691, Sweden, Department of Radiology, Aomori Rosai Hospital, Hachinohe, Aomori 031‑0822, Japan
Published online on: July 31, 2024 https://doi.org/10.3892/ol.2024.14604
Article Number: 471
Copyright: © Kikuchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is the most common cancer globally in terms of incidence. This cancer is classified into subtypes based on histological or immunological characteristics. HER2‑positive cases account for 15‑25% of breast cancer cases, and one of the first events in breast carcinogenesis is HER2 upregulation. Furthermore, HER2 expression increases the detection rate of metastatic or recurrent breast cancers by 50‑80%. The epidermal growth factor receptor family includes HER2, which is a transmembrane receptor protein. In our previous case report, patients who were resistant to anti‑HER2 monoclonal antibody therapy, chemotherapy and radiotherapy had higher concentrations of phospholipid metabolites such as phosphatidylcholine and sphingomyelin (SM), which was associated with cancer recurrence progression. To better understand the relationship between radiotherapy resistance and SM expression, breast cancer cell lines with and without HER2 expression (MCF7 and BT474) after exposure to ionizing radiation (IR) were examined. In the cell culture supernatant, similar levels of SM in MCF7 cells were identified after 1‑4 Gy exposure. However, SM levels in BT474 cells were upregulated compared with those of in the control group. Intracellular SM levels were upregulated in BT474 cells exposed to 1 and 4 Gy compared with the non‑irradiated control group. Furthermore, significantly increased mRNA expression levels of sphingomyelin synthase 2 (SGMS2) in BT474 cells exposed to IR were observed compared with those in nonirradiated cells; however, the SGMS2 levels in MCF7 cells did not differ significantly among the 0, 2 and 4 Gy groups. These findings suggested that a higher dose of IR induced the secretion of SM and its associated gene expression in HER2‑positive breast cancer cells.

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