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HMGA2 gene is a promising target for ovarian cancer silencing therapy
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| Zeitschriftentitel: | International Journal of Cancer |
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| Personen und Körperschaften: | , , , , , , |
| In: | International Journal of Cancer, 123, 2008, 2, S. 348-356 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>Ovarian cancer is one of the most lethal gynecological malignancies and the small success rate of routine therapeutic methods justifies efforts to develop new approaches. Evaluation of targets for effective inhibition of ovarian cancer cell growth should precipitate clinical application of gene silencing therapy. In our previous work, we showed upregulation of <jats:italic>HMGA2</jats:italic> gene expression as a result of Ras‐induced rat ovarian surface epithelial cell transformation. This gene codes the HMGA2 protein, a member of the high‐mobility group AT‐hook (HMGA) family of nonhistone chromatin proteins. Genome‐wide studies revealed upregulation of the <jats:italic>HMGA2</jats:italic> gene in human ovarian carcinomas. Herein we have evaluated over‐expression of the <jats:italic>HMGA2</jats:italic> gene, relevant to ovarian cancer, in subsets of human specimens and cell lines by <jats:italic>in situ</jats:italic> RNA hybridization and RT‐PCR. Transient silencing of <jats:italic>HMGA2</jats:italic> gene by means of siRNA inhibited proliferation of those ovarian cancer cells, which over‐express this gene initially. Growth suppression was mediated by cell‐cycle arrest. Stable silencing of highly expressed <jats:italic>HMGA2</jats:italic> gene by shRNAi in A27/80, Ovcar‐3 and OAW‐42 ovarian cancer cell lines resulted in growth inhibition because of G1 arrest and increase of apoptosis as well. The tumor growth inhibition effect of <jats:italic>HMGA2</jats:italic> silencing for Ovcar‐3 cells was validated <jats:italic>in vivo</jats:italic>. Our findings revealed that the <jats:italic>HMGA2</jats:italic> gene represents a promising target for gene silencing therapy in ovarian cancer. © 2008 Wiley‐Liss, Inc.</jats:p> |
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| Umfang: | 348-356 |
| ISSN: |
0020-7136
1097-0215 |
| DOI: | 10.1002/ijc.23491 |