Heat shock protein 27 enhances the tumorigenicity of immunogenic rat coloncarcinoma cell clones

The REG and PRO cell clones were obtained from a colon adenocarcinoma induc ed in a BDIX rat by 1,2-dimethylhydrazine. When injected s,c, into syngenei c hosts, REG cells induce tumors that regress in less than 3 weeks, whereas PRO cells, like parental cells, induce progressive tumors. Here, we show t hat compared to PRO cells, REG cells are more sensitive to cell death induc ed by anticancer drugs, The small heat shock protein (HSP) 27 is not expres sed or inducible in REG clones, whereas it is abundantly expressed and indu cible by heat shock in PRO clones. The expression of HSP27 in REG cells inc reases their resistance to apoptosis in vitro and dramatically enhances the ir tumorigenicity when injected s,c, into syngeneic rats. HSP27 expression in REG cells both increases tumor size and delays tumor regression. This in creased tumorigenicity is associated with a substantial decrease of in vivo tumor cell apoptosis. We conclude that HSP27 expression in malignant cells increases their tumorigenicity in syngeneic animals. In combination with t he role of HSP27 in tumor cell resistance to cytotoxic agents, its contribu tion to tumorigenicity makes this protein a potential target for antitumora l therapy.