The effects of hyperthermia on the expression of p53, the apoptosis-associated 
genes Bax and Bcl-2, Notch and S100A4 have been studied in the HepG2 cell line 
and the HUT cell line derived from HepG2, adapted for growth in hyperthermic 
conditions. Hyperthermia inhibits cell proliferation and induces apoptosis. 
HepG2 and HUT cells differed in respect of anchorage to growth surface, degree 
of proliferation and apoptosis and expression of p53, Bax, Bcl-2, Notch, and 
S100A4 genes. The induction of apoptosis and the inhibition of cell 
proliferation occurred independently of p53, and independently also of 
involvement of the apoptosis family genes Bax and Bcl-2. We demonstrate novel 
and marked differences between transient heat shock and heat adaptation in 
respect of pathways of signaling and generation of phenotypic effects in vitro. 
Different signaling patterns have been identified here. Pathways of signaling by 
S100A4, by its interaction with and sequestration of p53, and by Notch also seem 
differentially operational in the induction of apoptosis, and both appear to be 
activated as alternative pathways in the context of hyperthermia signaling 
independently of p53.