Abstract 3843: The potential of heat shock proteins 70/90 as molecular therapeutic targets in breast cancer

Abstract

Abstract Purpose: Heat shock proteins (hsps) are molecular chaperones that are synthesized by cells in response to various stress conditions. The expression of hsps have been shown to be associated with carcinogenesis and the expression of hsps have been implicated in the biological behavior of tumors. Recently, hsps have emerged as novel molecular targets in anticancer protocols. The objectives of this study were to investigate the significance of hsp 70/90 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. Methods: Breast tissues from 82 patients were obtained between January 2010 and December 2010 at the Division of Breast & Endocrine Surgery, Hallym University Sacred Heart Hospital. Expression of hsp 70/90 was studied by immunohistochemistry (IHC) on tissue sections from 63 breast carcinomas and 19 benign breast tissues. Both cytoplasmic and nuclear expression was measured. Expression of hsp 70/90 was also analyzed by use of a Western blot with the breast cancer cell lines. We next investigated the effects of blockers of hsp 70/90 on cell growth of the human breast cancer cell lines. Results: More prominent hsp 90 expression was observed in malignant tissue than in benign tissue by both cytoplasmic and nuclear IHC staining (p<0.001, p<0.001). Nuclear hsp 90 expression was associated with a positive lymph node status (p=0.003) and the presence of poorly differentiated tumors (p=0.028). 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 70/90. 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. Conclusion: 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. Citation Format: Ho Young Kim, Sanghwa Kim, Lee Su Kim. The potential of heat shock proteins 70/90 as molecular therapeutic targets in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3843.