Pathophysiological mechanism through the regulation of the transcriptional factor, c-fos, gene expression.

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1) Elevation of c-fos gene and AP-1 activity induced by stressesAlthough it has been widely accepted that the c-fos gene, which is responsive to various stresses, does not harbor the heat shock element (HSE) in its upstream region, we found the consensus-sequence for the HSE in the human, rat and mouse genes (BBRC 254:566, 1999). Since rostaglandin A1 (PGA1) increases heat shock element (HSE)-mediated transcription, thereby enhancing expression of HSE-bearing genes, including heat shock proteins, we hypothesized that PGA1 might increase c-fos expression through the HSE. Following investigation has revealed that c-fos expression at least partly by increasing the binding between heat shock factor-1 and the HSE, and that PGA1 enhances activity of activating protein-1 (AP-1). Interestingly, so far as PGA1 is present in the medium, AP-1-mediated transcription enhanced by PGA1 cannot be detected by the standard luciferase reporter gene assay. Instead, it can be detected by either checking lu … More ciferase mRNA levels in the presence of PGA1 or measuring luciferase activities just after removal of PGA1. These results shows that protein products of some stress-responsive genes can increase, not during the stressful condition, but immediately after recovery from stress(MCE 164:77, 2000).2) Detection of environmental hormone-like substancesIn the process of the studies on HSE, we have been interested in estrogenic activity because it can enhance expression of c-fos gene as well as heat shock proteins. Since we often experienced troubles with the assay for luciferase in control dishes, we got suspicious of the existence of hormone-like substances with estrogenic activity released from the culture dishes. Our experiments reveals that many types of polystyrene dishes release estrogenic impurities, a property that should be taken into account when carrying out research using estrogen-responsive cells or studying the cellular effects of this hormone and its analogs (Nature Biotechnology 19:812, 2001). Less