The role of heat shock protein 90/70 as potential molecular therapeutic targets in breast cancer Free

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Heat shock proteins (hsps) are molecular chaperones synthesized in response to various stress conditions. The expression of hsps have been shown to be associated with carcinogenesis and the expressions of hsps have been implicated in the biologic behavior of tumors. Recently, hsps have emerged as novel molecular targets in anticancer protocols. The objective of this study was to investigate the significance of hsp 90/70 in breast carcinogenesis and effect of geldanamycin (a blocker of hsp 90) and quercetin (a blocker of hsp 70) on growth inhibition in different breast cancer cell lines.
 Breast tissues from 82 patients were obtained, and expression of hsp 90/70 was studied by immunohistocemistry (IHC) on tissue sections from 63 breast carcinomas and 19 benign breast tissues. Both cytoplasmic and nuclear expressions were measured. Expression of hsp 90/70 was analyzed by Western blot in breast cancer cell lines and the growth inhibitory effects of hsp blockers were investigated.
 More prominent hsp 90 expression was observed in malignant tissue than in benign tissue by both cytoplasmic and nuclear IHC staning. Nuclear hsp 90 expression was associated with a positive lymph node status and the presence of poorly differentiated tumors. Expression of hsp 70 was not different in malignant and benign tissues as determined by both cytoplasmic and nuclear IHC staining. The breast cancer cell lines all expressed hsp 90/70. Geldanamycin markedly inhibited the cell growth of these breast cancer cell lines in a dose-dependent manner and induced apoptosis in the cell lines. Quercetin inhibited cell growth of the cell lines less efficiently.
 The expression of hsp 90 was associated with breast carcinogenesis and the presence of more aggressive tumors. Geldanamycin inhibited cell growth of hsp 90 expressing breast cancer cell lines. We suggest that hsp 90 may be a possible molecular target against breast cancer.