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

Int J Radiat Biol. 2012 Oct;88(10):688-93. doi: 10.3109/09553002.2012.706358. Epub 2012 Jul 20.

Abstract

Purpose: 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.

Materials and methods: 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).

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • DNA Damage
  • DNA Repair / radiation effects*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Side-Population Cells / metabolism
  • Side-Population Cells / pathology
  • Side-Population Cells / radiation effects
  • Signal Transduction / radiation effects

Substances

  • Fibroblast Growth Factor 2