Chk1 suppression leads to a reduction in the enhanced radiation-induced invasive capability on breast cancer cells. (14th June 2021)

• Record Type: Journal Article
• Authors: Adachi, Takanori; Zhao, Wantong; Minami, Kazumasa; Yokoyama, Yuhki; Okuzaki, Daisuke; Kondo, Rika; Takahashi, Yutaka; Tamari, Keisuke; Seo, Yuji; Isohashi, Fumiaki; Yamamoto, Hirofumi; Koizumi, Masahiko; Ogawa, Kazuhiko
• Is Part Of: Journal of radiation research. Volume 62:Number 5(2021)
• Page Start: 764
• Page End: 772
• Publication Date: 2021-06-14
• Subjects: γ-ray -- invasion -- Chk1 inhibitor -- breast cancer; Radiology, Medical -- Periodicals; Radiobiology -- Periodicals; Radiation -- Periodicals; 616.0757
• DOI: 10.1093/jrr/rrab049
• Languages: English
• ISSNs: 0449-3060

Abstract

Abstract: Radiation therapy is generally effective for treating breast cancers. However, approximately 30% of patients with breast cancer experience occasional post-treatment local and distant metastasis. Low-dose (0.5 Gy) irradiation is a risk factor that promotes the invasiveness of breast cancers. Although an inhibitor of checkpoint kinase 1 (Chk1) suppresses the growth and motility of breast cancer cell lines, no study has investigated the effects of the combined use of a Chk1 inhibitor and radiation on cancer metastasis. Here, we addressed this question by treating the human breast cancer cell line MDA-MB-231 ( in vitro ) and mouse mammary tumor cell line 4 T1 ( in vitro and in vivo ) with γ-irradiation and the Chk1 inhibitor PD407824. Low-dose γ-irradiation promoted invasiveness, which was suppressed by PD407824. Comprehensive gene expression analysis revealed that low-dose γ-irradiation upregulated the mRNA and protein levels of S100A4, the both of which were downregulated by PD407824. We conclude that PD407824 suppresses the expression of S100A4. As the result, γ-irradiation-induced cell invasiveness were inhibited.