Transforming growth factor-beta is an endogenous radioresistance factor in the esophageal adenocarcinoma cell line OE-33.
Transforming growth factor (TGF)-beta has profound effects on epithelial cell differentiation and is capable of modulating the response to exposure to ionizing radiation. We recently reported that TGF-beta downregulates c-myc mRNA expression and inhibits the growth of OE-33 esophageal carcinoma cells in vitro. These studies investigate the role of TGF-beta in the in vitro radiation response of OE-33 and four other human esophageal cancer cell lines. TGF-beta enhanced radioresistance of OE-33 cells, but did not affect the radiosensitivity of either of the two other adenocarcinoma cell lines BIC1 and SEG1 or of squamous carcinomas KYSE and OE-21. The TGF-beta enhanced radioresistance phenotype was associated with induced G0/G1 cell cycle arrest and upregulation of the G1 cyclin-dependent kinase inhibitor p27kip1 as well as downregulation of c-myc protein expression. Comparison of the relative radiosensitivities of untreated cells suggested that OE-33 (SF2 = 0.71) cells were inherently more radioresistant than BIC1 or SEG1 cells (SF2 = 0.6 and 0.56, respectively). Conditioned medium obtained from unirradiated OE-33 cells enhanced radioresistance compared with fresh medium. This enhancement was abrogated by preincubation of conditioned medium with a neutralizing anti-TGF-beta antibody suggesting endogenous TGF-beta production by OE-33 cells. Enzyme-linked immunoabsorbent assays revealed that exposure to ionizing radiation increased TGF-beta production in all five cell lines. These results suggest that TGF-beta acts as an endogenous, radiation-inducible radioresistance factor in OE-33 esophageal carcinoma cells.
Kim
Albert H
AH
Department of Radiation Oncology, Massey Cancer Center and Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0058, USA.
Lebman
Deborah A
DA
Dietz
Christopher M
CM
Snyder
Steven R
SR
Eley
Kerry W
KW
Chung
Theodore D
TD
D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D002277:Carcinoma / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000532:radiotherapy*; D005434:Flow Cytometry; D016193:G1 Phase; D006801:Humans; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D017077:Culture Media, Conditioned; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27