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The Small Heat Shock Protein hsp27 Is Correlated with Growth and Drug Resistance in Human Breast Cancer Cell Lines¹

University of Texas Health Science Center, Department of Medicine, Oncology, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7884

³ To whom correspondence should be addressed, at Department of Medicine/Oncology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7884.

An emerging body of evidence suggests that the heat shock proteins (hsp) may be involved in drug resistance. When hsp are induced by elevated temperatures, resistance to doxorubicin (Dox), but not to other commonly used chemotherapeutic agents, is induced in breast cancer cells. To evaluate the role of hsp27 in this phenomenon, we have transfected MDA-MB-231 breast cancer cells, which normally express low levels of hsp27, with a full-length hsp27 construct. These hsp27-overexpressing cells now display a 3-fold elevated resistance to Dox. Anchorage-dependent proliferation and anchorage-independent growth were also increased 2-4-fold in these transfectants. We have also derived a MCF-7 breast cancer cell line with amplified endogenous hsp27 which is highly resistant to Dox. When these cells are transfected with an antisense hsp27 construct, they are rendered sensitive to Dox (3-fold) with anchorage-dependent as well as anchorage-independent growth, similarly decreased. These results suggest that hsp27 specifically confers Dox resistance in human breast cancer cells and, furthermore, that hsp27 may be involved in the regulation of cell growth.

¹ This work was supported by NIH Grant CA11378, a Cancer Center support grant from the National Cancer Institute CA 54174, and NIH Grant CA58183-01.

² S. O. is a recipient of a postdoctoral fellowship from Deutscher Akademischer Austauschdienst and from the Susan G. Komen Foundation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/ 7/93. Accepted 8/18/93.

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