Silencing human epidermal growth factor receptor‐3 radiosensitizes human luminal A breast cancer cells. Issue 12 (22nd October 2018)

• Record Type: Journal Article
• Authors: He, Guofeng; Di, Xiaoke; Yan, Jingjing; Zhu, Caiqiang; Sun, Xinchen; Zhang, Shu
• Is Part Of: Cancer science. Volume 109:Issue 12(2018)
• Page Start: 3774
• Page End: 3782
• Publication Date: 2018-10-22
• Subjects: HER3 -- ionizing radiation -- luminal A breast cancer -- mechanism -- radiosensitivity; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13810
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Endocrine therapy and radiotherapy are the main treatments for luminal A breast cancer. However, drug and radiotherapy resistance could occur during long‐term treatment, leading to local recurrence and distant metastasis. Some studies have found that drug resistance might be related to human epidermal growth factor receptor‐3 (HER3) overexpression. However, whether HER3 plays a role in radiotherapy resistance is unknown. The purpose of this study is to elucidate the effect of HER3 in radiotherapy and to assess whether HER3 could be a potential target for radiosensitivity. We used retroviruses to construct stable low expression of HER3 in MCF‐7 and ZR75‐1cells. The CCK‐8 assay was used to observe proliferation. Colony‐forming assay was used to detect radiosensitivity. Flow cytometry was used to observe the cell cycle and apoptosis. Immunofluorescence assay was used to detect the number of γH2AX foci in the nucleus with or without ionizing radiation (IR). Western blot analysis was used to verify the change of relative proteins. Nude mice were used to observe tumor growth in vivo. In our study, silencing HER3 reduced cell proliferation and clone formation ability after IR, so silencing HER3 increased the sensitivity of luminal A breast cancer cells to radiotherapy. In terms of radiosensitivity mechanisms, it is suggested that the silencing of HER3 enhanced IR‐induced DNA damage, reduced DNA repair, and increased apoptosis and G2 /M arrest. In addition, silencing HER3 combined with IR clearly inhibited the transplanted tumor growth in vivo. Therefore, we concluded that HER3 played a role in radiotherapy resistance. Silencing HER3 increased the radiosensitivity of luminal A breast cancer cells and HER3 could be a potential target for radiosensitivity. Abstract : The purpose of this study is to elucidate the effect of human epidermal growth factor receptor‐3 (HER3) in radiotherapy resistance and further assess whether HER3 could be a potential target for radiosensitivity. We concluded that silencing HER3 could significantly increase the radiosensitivity of luminal A breast cancer cells and HER3 could be a potential target for radiotherapy.