Differential Induction of Hsp70-encoding Genes in Human
Hematopoietic Cells*
Sirpa
Leppä
§¶,
Risto
Kajanne§,
Laura
Arminen§, and
Lea
Sistonen
**
From the Department of Oncology, Helsinki University
Central Hospital, P.O. Box 180, Helsinki FIN-00029 HUCH, Finland,
§ Molecular Cancer Biology Research Program, Biomedicum
Helsinki and Haartman Institute, P.O. Box 63, University of Helsinki,
Helsinki FIN-00014, Finland, Turku Centre for Biotechnology,
University of Turku, Åbo Akademi University, P.O. Box 123, Turku
FIN-20521, Finland, and the ** Department of
Biology, Åbo Akademi University, P.O. Box 2, Turku FIN-20521, Finland
The rapid transcriptional activation of heat
shock genes in response to stress is crucial for the cellular survival
and the development of thermotolerance. Although heat shock response is a widespread phenomenon, certain cells exhibit a diminished induction of heat shock gene expression upon stress stimuli. Here we have analyzed the development of thermotolerance and induction of distinct Hsp70 encoding genes in three cell lines representing different hematopoietic cell types. We show that in response to heat shock, cell
survival and induction of thermotolerance are impaired in Raji and HL60
cells, as compared with K562 cells. Accordingly, transcriptional
induction of the hsp70 gene is diminished in Raji and HL60 cells. This
appears to be due to inability of transcription factors, including HSF1
to bind to the hsp70.1 promoter in vivo. Consistent with
the genomic footprint, analysis of hsp70.1 mRNA expression using a
specific 3'-untranslated region probe reveals that induction of the
hsp70.1 gene upon heat shock is completely abolished in Raji and HL60
cells. The suppression of the hsp70.1 promoter is not caused by
impaired function of HSF1, since HSF1 is equally activated in all cell
types and occupies another heat-inducible promoter, hsp90
.
Furthermore, among distinct inducible hsp70 genes, suppression seems to
be specific for the hsp70.1 gene, since heat shock results in induction
of hsp70.2 and hsp70B' mRNA expression in all cell lines. Taken
together, our results demonstrate that distinct Hsp70-encoding genes
contribute to the heat shock response in a cell
type-dependent manner.
*
The work was supported by grants from the Academy of Finland
(to S. L. and L. S), the Finnish Cancer Organizations (to S. L. and
L. S), the Finnish Cultural Foundation (to S. L.), Helsinki Biocentrum (to S. L.), and the Sigrid Juselius Foundation (to L. S.).
¶
To whom correspondence may be addressed: Molecular Cancer
Biology Research Program, Biomedicum Helsinki, P.O. Box 63, University of Helsinki, Helsinki FIN-00014, Finland. Tel.: 358-9-19125606; Fax:
358-9-19125554; E-mail: sirpa.leppa@helsinki.fi.
To whom correspondence may be addressed: Turku Centre for
Biotechnology, P.O. Box 123, Turku FIN-20521, Finland. Tel.:
358-2-333-8028; Fax: 358-2-333-8000; E-mail:
lea.sistonen@btk.utu.fi.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
