Over-expression of heat shock protein 70 in mice is associated with growth retardation, tumor formation, and early death.
Experiments in lower organisms, such as worms and flies, indicate that the molecular chaperone protein heat shock protein 70 (HSP70) is a longevity factor. In contrast, we demonstrate here that mice overexpressing HSP70 display growth retardation and early death. HSP70 transgenic mice displayed increased levels of serum corticosterone and weaker expression and activity of the glucocorticoid receptor in the liver. Serum insulin-like growth factor-1 (IGF-1) concentrations in the transgenic mice were 50% lower than in the control mice, leading to growth retardation. HSP70 transgenic mice showed decreased expression of Casp9, which encodes caspase-9, and increased expression of the anti-apoptotic Bcl-2 gene, indicating that apoptosis is suppressed. Consequently, most of the transgenic animals died before the age of 18 months from tumors in their lungs and lymph nodes. We suggest that the proinflammatory and antiapoptotic effects of HSP70 might be responsible for the growth retardation, tumor formation, and early death observed in the HSP70 transgenic mice.
Vanhooren
Valerie
V
Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
Liu
Xue-En
XE
Desmyter
Liesbeth
L
Fan
Ye-Dong
YD
Vanwalleghem
Lieve
L
Van Molle
Wim
W
Dewaele
Sylviane
S
Praet
Marleen
M
Contreras
Roland
R
Libert
Claude
C
Chen
Cuiying
C
D000818:Animals; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D003345:Corticosterone / Q000097:blood; D005260:Female; D015870:Gene Expression; D006130:Growth Disorders / Q000209:etiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D007334:Insulin-Like Growth Factor I; D053453:Caspase 9; D003345:Corticosterone