CEA, iRCM, Laboratoire de Génomique et Radiobiologie de la Kératinopoïèse, Evry, France.
Int J Radiat Biol. 2012 Oct;88(10):688-93. doi: 10.3109/09553002.2012.706358. Epub 2012 Jul 20.
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.
成纤维细胞生长因子 2(FGF2)是一种众所周知的存活因子。然而,其在 DNA 修复中的作用尚未得到充分证实。本研究旨在研究表皮癌细胞中 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)。采用碱性彗星试验评估辐射诱导的 DNA 损伤和修复。通过酶联免疫吸附试验(ELISA)定量 FGF2 的表达。
SP 细胞表现出辐射诱导的 DNA 损伤的快速修复,以及核 FGF2 的高基础水平。阻断 FGF2 信号转导可消除快速 DNA 修复。相比之下,在 MP 细胞中,损伤修复较慢,基础表达的 FGF2 水平较低。此外,外源性 FGF2 可加速 MP 细胞中的 DNA 修复。SP 细胞在受到照射时会分泌 FGF2,而 MP 细胞则不会。
在表皮癌细胞中发现 FGF2 介导 DNA 修复。我们推测,癌干细胞由于核 FGF2 的高基础水平而内在地被激活以快速修复 DNA 损伤。相比之下,低 FGF2 含量的主群表现出较低的修复率,外源性 FGF2 可增加其修复率。