Heat induction of reporter gene expression via the gadd153 promoter and its possible application to hyperthermia treatment of cancer

The use of the gadd153 promoter to induce expression of a reporter gene under heat stress conditions was investigated, since the results of previous studies have suggested that the gadd153 promoter is likely to be activated by the indirect effects of hyperthermia, that is, by DNA damage that occurs when reactive oxygen species are produced by heat stress. The optimum temperature for a significant induction was found to be between 41 and 43 degrees C and increased expression of the reporter gene was observed at about 24 h after the heat treatment. Under these conditions, the cell integrity was not altered morphologically and the growth stopped temporarily, while the viability was maintained. A second increase in expression occurred at a later stage when the cells were severely damaged at 43-45 degrees C. At these temperatures, the cellular morphology showed significant alteration and the growth was strongly arrested. This is likely to be due to a different mechanism which could involve DNA repair processes. It is expected that this method of induction can be exploited to drive the production of a protein of interest in a cancer treatment program that includes hyperthermia.