Open AccessSilencing human epidermal growth factor receptor‐3 radiosensitizes human luminal A breast cancer cells
Author(s) -
He Guofeng,
Di Xiaoke,
Yan Jingjing,
Zhu Caiqiang,
Sun Xinchen,
Zhang Shu
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13810
Subject(s) - radiosensitivity , gene silencing , cancer research , biology , cell cycle , apoptosis , cell growth , epidermal growth factor receptor , radiation therapy , epidermal growth factor , breast cancer , radioresistance , flow cytometry , in vivo , metastasis , cancer , cell culture , microbiology and biotechnology , medicine , biochemistry , genetics , gene
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 ( HER 3) overexpression. However, whether HER 3 plays a role in radiotherapy resistance is unknown. The purpose of this study is to elucidate the effect of HER 3 in radiotherapy and to assess whether HER 3 could be a potential target for radiosensitivity. We used retroviruses to construct stable low expression of HER 3 in MCF ‐7 and ZR 75‐1cells. 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 γH2 AX 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 HER 3 reduced cell proliferation and clone formation ability after IR , so silencing HER 3 increased the sensitivity of luminal A breast cancer cells to radiotherapy. In terms of radiosensitivity mechanisms, it is suggested that the silencing of HER 3 enhanced IR ‐induced DNA damage, reduced DNA repair, and increased apoptosis and G 2 /M arrest. In addition, silencing HER 3 combined with IR clearly inhibited the transplanted tumor growth in vivo. Therefore, we concluded that HER 3 played a role in radiotherapy resistance. Silencing HER 3 increased the radiosensitivity of luminal A breast cancer cells and HER 3 could be a potential target for radiosensitivity.