FGF2 mediates DNA repair in epidermoid carcinoma cells exposed to ionizing radiation.

FGF2 mediates DNA repair in epidermoid carcinoma cells exposed to ionizing radiation.
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DOI:
10.3109/09553002.2012.706358
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发表时间:
2012-10
影响因子:
2.6
通讯作者:
Martin MT
Martin MT
中科院分区:
医学3区
文献类型:
--
作者:
Marie M;Hafner S;Moratille S;Vaigot P;Mine S;Rigaud O;Martin MT

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成纤维细胞生长因子 2 (FGF2) 是众所周知的生存因子。然而,其在 DNA 修复中的作用却鲜有记录。本研究旨在研究表皮样癌细胞中 FGF2 在 DNA 修复中的潜在作用。从人 A431 鳞状癌细胞中分离出具有癌症干细胞样特性的侧群 (SP) 和主群 (MP)。使用碱性彗星测定评估辐射诱导的 DNA 损伤和修复。通过酶联免疫吸附测定(ELISA)对 FGF2 表达进行定量。 SP细胞表现出对辐射引起的DNA损伤的快速修复和高组成型核FGF2水平。阻断 FGF2 信号传导会破坏 DNA 的快速修复。相反,在 MP 细胞中,损伤修复速度较慢与 FGF2 基础表达低相关。此外,添加外源FGF2可加速MP细胞中的DNA修复。当受到辐射时,SP 细胞分泌 FGF2,而 MP 细胞则不分泌。 FGF2被发现可以介导表皮样癌细胞中的DNA修复。我们假设癌干细胞本质上会通过高水平的核 FGF2 快速修复 DNA 损伤。相比之下,FGF2 含量低的主要群体表现出较低的修复率,而外源性 FGF2 可以提高修复率。
Fibroblast growth factor 2 (FGF2) is a well-known survival factor. However, its role in DNA repair is poorly documented. The present study was designed to investigate in epidermoid carcinoma cells the potential role of FGF2 in DNA repair. The side population (SP) with cancer stem cell-like properties and the main population (MP) were isolated from human A431 squamous carcinoma cells. Radiation-induced DNA damage and repair were assessed using the alkaline comet assay. FGF2 expression was quantified by enzyme linked immunosorbent assay (ELISA). SP cells exhibited rapid repair of radiation induced DNA damage and a high constitutive level of nuclear FGF2. Blocking FGF2 signaling abrogated the rapid DNA repair. In contrast, in MP cells, a slower repair of damage was associated with low basal expression of FGF2. Moreover, the addition of exogenous FGF2 accelerated DNA repair in MP cells. When irradiated, SP cells secreted FGF2, whereas MP cells did not. FGF2 was found to mediate DNA repair in epidermoid carcinoma cells. We postulate that carcinoma stem cells would be intrinsically primed to rapidly repair DNA damage by a high constitutive level of nuclear FGF2. In contrast, the main population with a low FGF2 content exhibits a lower repair rate which can be increased by exogenous FGF2.
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