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1 January 2003 Hsp25 and Hsp70 in rodent tumors treated with doxorubicin and lovastatin
Daniel R. Ciocca, Viviana R. Rozados, F. Darío Cuello Carrión, Silvia I. Gervasoni, Pablo Matar, O. Graciela Scharovsky
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Heat shock protein 27 (Hsp27) and Hsp70 have been involved in resistance to anticancer drugs in human breast cancer cells growing in vitro and in vivo. In this study, we examined the expression of Hsp25 (the rodent homologue to human Hsp27) and Hsp70 in 3 different rodent tumors (a mouse breast carcinoma, a rat sarcoma, and a rat lymphoma maintained by subcutaneous passages) treated in vivo with doxorubicin (DOX) and lovastatin (LOV). All tumors showed massive cell death under control untreated conditions, and this massive death increased after cytotoxic drug administration. In this study, we show that this death was due to classic apoptosis. The tumors also showed isolated apoptotic cells between viable tumor cells, and this occurred more significantly in the lymphoma. The tumor type that was more resistant to cell death was the sarcoma, and this was found in sarcomas growing both under control conditions and after cytotoxic drug administration. Moreover, sarcomas showed the highest expression levels of Hsp25 in the viable tumor cells growing under untreated conditions, and these levels increased after DOX and LOV administration. After drug treatment, only sarcoma tumor cells showed a significant increase in Hsp70. In other words, sarcomas were the tumors with lower cell death, displayed a competent Hsp70 and Hsp25 response with nuclear translocation, and had the highest levels of Hsp25. In sarcomas, Hsp25 and Hsp70 were found in viable tumor cells located around the blood vessels, and these areas showed the most resistant tumor cell phenotype after chemotherapy. In addition, Hsp25 expression was found in endothelial cells as unique feature revealed only in lymphomas. In conclusion, our study shows that each tumor type has unique features regarding the expression of Hsp25 and Hsp70 and that these proteins seem to be implicated in drug resistance mainly in sarcomas, making these model systems important to perform more mechanistic studies on the role of Hsps in resistance to certain cytotoxic drugs.

Daniel R. Ciocca, Viviana R. Rozados, F. Darío Cuello Carrión, Silvia I. Gervasoni, Pablo Matar, and O. Graciela Scharovsky "Hsp25 and Hsp70 in rodent tumors treated with doxorubicin and lovastatin," Cell Stress & Chaperones 8(1), 26-36, (1 January 2003).<26:HAHIRT>2.0.CO;2
Received: 9 April 2002; Accepted: 1 September 2002; Published: 1 January 2003

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