Life and Medical Sciences
Cell & Developmental Biology
Wiley InterScience Backfile Collection 1832-2000
Low, mitogenic fluences of UVC (3.7-5.6 Jm-2) have previously been shown to cause increases of radioimmunoassayable transforming growth factor alpha (TGFα) in the medium and cells of cultures of melanocytes, melanoma lines, and HeLa cells (Ellem, K.A.O., Cullinan, M., Baumann, K.C., Dunstan, A.: Carcinogenesis 9:797-801, 1988). Here the cellular mechanism of this increase is explored by Northern blotting to detect any changes in TGFα mRNA levels, and the use of inhibitors of macromolecular synthesis to attempt to block the increase in TGFα protein. We were unable to detect any increase in TGFα mRNA levels attributable to UVC between 2 and 24 hours after irradiation. Inhibition of DNA synthesis (arabinosylcytosine, 10 μM), RNA synthesis (actinomycin D, 3 μg/ml; DRB 93 μM), or protein synthesis (cycloheximide, 10 μg/ml) failed to prevent the UVC induced increase in TGFα. We conclude that the UVC induction of TGFα is by a posttranslational mechanism. There was considerable discordance between the amount of TGFα protein and its mRNA in cultures of 15 different melanoma cell lines, which again emphasized that posttranscriptional mechanisms modulate the release of immunodetectable TGFα. We also found that the inhibitors themselves were capable of inducing an increase in TGFα in MM229 cultures. This suggests that the inhibitors and UV may effect the increase by a common mechanism, perhaps the activation of cell surface proteases as suggested for other stimuli (e.g., Pandiella, A., and Massagué, J.: Proc. Natl. Acad. Sci., USA 88:1726-1730, 1991) and that the response may be part of a global response to perturbation of DNA synthesis. © 1992 Wiley-Liss, Inc.
Type of Medium: