A NOVEL HEAT-SHOCK RESPONSE IN PROLACTIN-DEPENDENT NB2 NODE LYMPHOMA-CELLS

Virtually all cells respond to heat stress by increased expression or induction of one or more of the highly conserved cellular stress respo nse proteins, heat shock proteins (HSPs). Here, we report the unusual property of rat Nb2-11 cells, a prolactin-dependent pre-T cell line, t o display reduced HSP expression following exposure to elevated temper ature. After heat stress (41 degrees C, 1 h), there was no evidence of inducible members of the 70 kDa HSP family, a response common to othe r cell culture and tissue systems. Moreover, expression of constitutiv e members of the HSP70 and HSP90 families decreased during the heat st ress, apparently reflecting a decrease in mRNA stability. Gel shift as says revealed that heat shock factor (HSF) was activated in spite of t he lack of expression of inducible HSP70 transcripts, although its DNA binding rapidly deteriorated. Immunoblotting, using an antibody speci fic to HSF1, indicated that proteolysis of HSF1 may be responsible for this rapid termination of heat shock element binding. CCAAT binding, a component of constitutive HSP70 expression, was also reduced by heat stress in Nb2-11 cells and may account for the decline in constitutiv e HSP70 expression. Prolactin pretreatment prevented the fragmentation of HSF1, protected heat shock element and CCAAT binding, prevented th e decline in constitutive HSP70 and HSP90 expression, and restored a m odest expression of inducible HSP70 following heat treatment. Results of this study describe a unique regulatory defect in HSP expression in Nb2-11 cells, possibly a common characteristic of other hormone-depen dent tumors.