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- Title
Chk1 suppression leads to a reduction in the enhanced radiation-induced invasive capability on breast cancer cells.
- 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
- 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.
- Subjects
RADIATION; CANCER cells; BREAST cancer
- Publication
Journal of Radiation Research, 2021, Vol 62, Issue 5, p764
- ISSN
0449-3060
- Publication type
Article
- DOI
10.1093/jrr/rrab049