Transforming growth factor (TGF)-β has profound effects on epithelial cell differentiation and is capable of modulating the response to exposure to ionizing radiation. We recently reported that TGF-β downregulates c-myc mRNA expression and inhibits the growth of OE-33 esophageal carcinoma cells in vitro. These studies investigate the role of TGF-β in the in vitro radiation response of OE-33 and four other human esophageal cancer cell lines. TGF-β 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-β 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-β antibody suggesting endogenous TGF-β production by OE-33 cells. Enzyme-linked immunoabsorbent assays revealed that exposure to ionizing radiation increased TGF-β production in all five cell lines. These results suggest that TGF-β acts as an endogenous, radiation-inducible radioresistance factor in OE-33 esophageal carcinoma cells.

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