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源自转移灶的犬乳腺肿瘤细胞系显示RAD51表达增加,但通过抑制p21降低了放射抗性。

Canine Mammary Tumor Cell Lines Derived from Metastatic Foci Show Increased RAD51 Expression but Diminished Radioresistance via p21 Inhibition.

作者信息

Shimakawa Kei, Ochiai Kazuhiko, Hirose Sachi, Tanabe Eri, Michishita Masaki, Sakaue Motoharu, Yoshikawa Yasunaga, Morimatsu Masami, Tajima Tsuyoshi, Watanabe Masami, Tanaka Yoshikazu

机构信息

Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.

Research Center for Animal Life Science, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.

出版信息

Vet Sci. 2022 Dec 17;9(12):703. doi: 10.3390/vetsci9120703.

Abstract

Due to the high incidence of mammary tumors in dogs, it is important to elucidate the pathogenesis of these tumors in veterinary medicine. Radiation therapy is often used to treat mammary tumors that target DNA lesions. RAD51 is a key molecule that repairs DNA damage via homologous recombination. We examined the relationship between RAD51 expression and radiosensitivity in mammary tumor cell lines. CHMp and CHMm from the same individual were selected based on the differences in RAD51 expression. The radiosensitivity of both cell lines was examined using MTT and scratch assays; CHMm, which has high RAD51 expression, showed higher sensitivity to radiation than CHMp. However, the nuclear focus of RAD51 during DNA repair was formed normally in CHMp, but not in most of CHMm. Since irradiation resulted in the suppression of cell cycle progression in CHMp, the expression of p21, a cell cycle regulatory factor, was detected in CHMp after 15 Gy irradiation but not in CHMm. These results indicate that functional expression is more important than the quantitative expression of RAD51 in canine mammary tumor cells in response to DNA damage.

摘要

由于犬乳腺肿瘤的发病率较高,因此在兽医学中阐明这些肿瘤的发病机制很重要。放射治疗常用于治疗针对DNA损伤的乳腺肿瘤。RAD51是一种通过同源重组修复DNA损伤的关键分子。我们研究了RAD51表达与乳腺肿瘤细胞系放射敏感性之间的关系。根据RAD51表达的差异,从同一个体中选择了CHMp和CHMm。使用MTT和划痕试验检测了两种细胞系的放射敏感性;RAD51表达较高的CHMm对辐射的敏感性高于CHMp。然而,DNA修复过程中RAD51的核灶在CHMp中正常形成,而在大多数CHMm中则未形成。由于照射导致CHMp中的细胞周期进程受到抑制,因此在15 Gy照射后在CHMp中检测到细胞周期调节因子p21的表达,而在CHMm中未检测到。这些结果表明,在犬乳腺肿瘤细胞对DNA损伤的反应中,RAD51的功能性表达比定量表达更重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4963/9784702/49ac2bd34cf7/vetsci-09-00703-g001.jpg

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