Frequent loss of cystatin E M expression implicated in the progression of prostate cancer
Cystatin E/M ( CST6 ) is a natural inhibitor of lysosomal cysteine proteases. Recent studies have shown that experimental manipulation of CST6 expression alters the metastatic behavior of human breast cancer cells. However, the association of CST6 with prostate cancer invasion and progression remain...
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Published in | Oncogene Vol. 28; no. 31; pp. 2829 - 2838 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
06.08.2009
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Cystatin E/M (
CST6
) is a natural inhibitor of lysosomal cysteine proteases. Recent studies have shown that experimental manipulation of
CST6
expression alters the metastatic behavior of human breast cancer cells. However, the association of
CST6
with prostate cancer invasion and progression remains unclear. Here, we show that
CST6
is robustly expressed in normal human prostate epithelium, whereas its expression is downregulated in metastatic prostate cell lines and prostate tumor tissues. Treatment of metastatic prostate cell lines with the histone deacetylase inhibitor trichostatin A resulted in significant induction of
CST6
mRNA levels and increased
CST6
protein expression, indicating that epigenetic silencing may play a role in the loss of
CST6
expression observed in prostate cancer.
CST6
overexpression in human prostate cancer cells significantly reduced
in vitro
cell proliferation and matrigel invasion. Furthermore, the results from a bioluminescence tumor/metastasis model showed that the overexpression of
CST6
significantly inhibits tumor growth and the incidence of lung metastasis. These results suggest that the downregulation of the
CST6
gene is associated with promoter histone modifications and that this association plays an important role in prostate cancer progression during the invasive and metastatic stages of the disease. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/onc.2009.134 |