Journal
TUMOR BIOLOGY
Volume 27, Issue 1, Pages 17-26Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1159/000090152
Keywords
breast carcinoma; chaperokine; heat shock proteins; metastasis; siRNA
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Funding
- NCI NIH HHS [R01 CA091889, R01 CA091889-05] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA091889] Funding Source: NIH RePORTER
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The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration. Copyright (C) 2006 S. Karger AG, Basel.
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