BIOLOGICAL AND CLINICAL IMPLICATIONS OF HEAT-SHOCK PROTEIN 27000 (HSP27) - A REVIEW

Heat shock and other environmental and pathophysiologic stresses stimu late synthesis of heat shock proteins (Hsps). These proteins enable th e cell to survive and recover from stressful conditions by as yet unco mpletely understood mechanisms. Hsp27 is an important small Hsp (molec ular weight, 27000) found in human cells-both cancer cells and normal cells. This protein, besides its putative role in thermotolerance, is of special clinical interest because of recent data suggesting it may also play a role in drug resistance. In adults, Hsp27 is found particu larly in several cell types such as breast, uterus, cervix, placenta, skin, and platelets. Although low-molecular-weight (small) Hsps have b een found to be involved in embryogenesis of Xenopus and Drosophila, t hey have not been detected in human fetal organs. Regulation of expres sion of the Hsp gene (also known as HSPB1) has been considered a parad igm of gene regulation and is actively being studied in both prokaryot es and eukaryotes. In prokaryotes, the major Hsp genes are transcripti onally regulated by positively and negatively acting transcription fac tors. In eukaryotes, the genes encoding Hsps contain a regulatory DNA motif (inverted repeats of the pentameric sequence nGAAn) known as the heat shock element. Hsp27 may function as a molecular chaperone and i n signal transduction pathways of different cell regulators, and Hsp27 and other Hsps may be active in development of resistance to stressfu l conditions and agents including cytotoxic drugs. Study findings indi cate that some but not all estrogen-positive breast cancers express Hs p27, and overexpression of Hsp27 has been associated with both good an d poor prognosis. In endometrial carcinomas, the presence of Hsp27 is correlated with the degree of tumor differentiation as well as with th e presence of estrogen and progesterone receptors. Studies suggest, ho wever, that detection of Hsp27 should not be considered to be a method for identifying hormone-responsive tumors or detecting estrogen recep tors. Hsp27 seems to be a biochemical marker of estrogenic endometrial response. In patients with cervical cancer, Hsp27 is predominantly ex pressed in well-differentiated and moderately differentiated squamous cell carcinomas. In addition, expression of Hsp27 seems to be a negati ve prognostic factor for gastric cancer. Different isoforms of Hsp27 h ave been found in lymphoid tissue of patients with acute lymphoblastic leukemia, and the protein has also been associated with viral infecti ons. These aspects are summarized and discussed in the present review.