Mouse Cell Lines That Use Heat Shock Promoters to Regulate the Expression of Tissue Plasminogen Activator

Abstract

The promoters from Drosophila and human 70,000-dalton heat shock protein (hsp70) genes were linked to human tissue plasminogen activator (tPA) cDNA. Mouse C127 cells were transformed with bovine papilloma virus (BPV) vectors carrying the hybrid hsp70/tPA genes. Stable BPV-transformed cell lines were selected and analyzed for tPA expression before and after heat shock. In most cell lines, there was a low level of tPA production even in the absence of heat shock or other obvious stress. After heat shock (42 degrees C, 2 hr), there was up to a 40-fold increase in tPA production. Production of tPA protein occurred within the first 5 h after the heat shock and was due to a burst of hsp70/tPA transcription during the heat shock. The hsp70/tPA transcripts appeared to have a short half-life. Thus, stable mouse cell lines carrying hsp70/tPA hybrid genes can be induced by a short heat shock to transcribe high levels of hsp70/tPA mRNAs and, subsequently, to produce elevated levels of tPA protein.