PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 17 Induced Gene Expression
Room: Nevada Exhibition Center
(P22-247) TGF-
signaling and radiation response in lung cancer.
Sathishkumar, Sabapathi*,1, Alcock, Rachael1, Dey, Swatee1, Chendil, Damodaran2, Krishna, Andhal2, Parekh, Sagar1, Mohiuddin, Mohammed1, Ahmed, Mansoor1, 1 University of Kentucky, Lexington, KY2 University of Kentucky, Lexington, KY
ABSTRACT-
TGF-, a pleiotropic growth factor, elicits its growth inhibitory response in a variety of carcinoma cells by binding to cell surface heteromeric receptor complex RI and RII. TGF-signaling process recruits a complex downstream effector components including the Smad genes (Smad4/DPC-4) and CDK inhibitors. We hypothesize that the dysregulation of TGF-signaling, due to lack of RII or DPC-4 expression will cause an impact on radiation response. Three lung cancer cell lines were studied for their RII and DPC-4 gene expression status using western blot and RT-PCR. A549 and H460 are non-small lung carcinoma (NSCLC) cells and UKY-29 cell line was established at University of Kentucky from pleural effusion sample of a lung cancer patient. A549 and UKY-29 expressed both RII and DPC-4, whereas RII and DPC-4 expression was absent in H460 cells. Radiation caused induction of TGF-1 protein in A549 and UKY-29 but not in H460 cells. Radiation or recombinant TGF-(rhTGF-)- induced TGF-signaling was assessed in these cell lines by TGF-responsive promoter activity using 3TP-luciferase reporter assay. Radiation and rhTGF-caused induction of TGF-signaling (increased luciferase activity) in A549 and UKY-29 cells but not in H460 cells. These results suggest that lack of RII and DPC-4 expression in H460 caused inactivation of TGF-signaling. In addition, when compared to A549 and UKY-29 cells, H460 cells were resistant to radiation/rhTGF--induced apoptosis. Together, these data suggest that lack of TGF-signaling machinery may cause radio-resistant phenotype.
KEYWORDS: TGF-, lung cancer, RII, DPC4, radiation