Conclusions
Our findings imply that inhibition of radiation-induced TGF-beta signaling via abrogation of the RII function enhances the radio-resistance of normal lung epithelial cells, and this can be directly attributed to the loss of TGF-beta signaling function.
Purpose
To address the functional role of radiation-induced transforming growth factor-beta (TGF-beta) signaling in a normal epithelial background, we selected a spontaneously immortalized lung epithelial cell line derived from the normal lung tissue of a dominant-negative mutant of the TGF-beta RII (DeltaRII) transgenic mouse that conditionally expressed DeltaRII under the control of the metallothionein promoter (MT-1), and assessed this cell line's response to radiation.
Results
Exposure to ZnSO(4) inhibited TGF-beta signaling induced either by recombinant TGF-beta1 or ionizing radiation. The SILECC, treated with either ZnSO(4) or neutralizing antibody against TGF-beta, showed a significant increase in radio-resistance compared to untreated cells. Furthermore, the expression of DeltaRII inhibited the radiation-induced up-regulation of the TGF-beta effector gene p21(waf1/cip1). Conclusions: Our findings imply that inhibition of radiation-induced TGF-beta signaling via abrogation of the RII function enhances the radio-resistance of normal lung epithelial cells, and this can be directly attributed to the loss of TGF-beta signaling function.