Expression of HSP27 results in increased sensitivity to tumor necrosis factor, etoposide, and H2O2 in an oxidative stress-resistant cell line

The role of HSP27 in cell growth and resistance to stress was investigated using murine fibrosarcoma L929 cells (normally devoid of constitutively exp ressed small HSPs) and human osteoblast-like SaOS-2 cells stably transfecte d with a human hsp27 expression vector. Our data showed that our L929 cells were more resistant to oxidative stress than generally observed for this l ine. Production of HSP27 in these cells led to a marked decrease in growth rate associated with a series of phenotypical changes, including cell sprea ding, cellular and nuclear hypertrophy, development of an irregular outline , and a tremendous accumulation of actin stress fibers. By contrast, none o f these changes was observable in SaOS-2/hsp27 transfectants overexpressing the protein product. Together, these observations are consistent with a ca use-to-effect cascade relationship between increased (or induced) HSP27 exp ression, changes in cytoskeletal organization, and decreased growth. On the other hand, whereas the transfection of the hsp27 gene increased the cell resistance to heat in both cell lines, only in SaOS-2 cells was this associ ated with protection to the cytotoxic action of tumor necrosis factor-alpha (TNF-alpha) and etoposide. Unexpectedly, L929/hsp27 transfectants exhibite d an increased sensitivity to both agents and also to H2O2. These data thus imply that different mechanisms are involved in the cell resistance to hea t shock and to the cytotoxic action of TNF-alpha, etoposide, and H2O2. They also plead against the simple view that overexpression of a phosphorylatab le HSP27 would necessarily be beneficial in terms of increased cell resista nce to any type of stress. Our data further indicate that the role of HSP27 in cellular resistance to stress and in cell proliferation involves differ ent targets and that the ultimate result of its interference with these pro cesses depends on the intracellular context in which the protein is express ed. J. Cell. Physiol. 177:606-617, 1998. (C) 1998 Wiley-Liss, Inc.