Antisense clusterin oligodeoxynucleotides increase the response of HER-2 gene amplified breast cancer cells to Trastuzumab.
| Title: | Antisense clusterin oligodeoxynucleotides increase the response of HER-2 gene amplified breast cancer cells to Trastuzumab. |
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| Authors: | Annamaria Biroccio1, Carmen D'Angelo1, Burkhard Jansen2, Martin E. Gleave2, Gabriella Zupi1 |
| Source: | Journal of Cellular Physiology. Aug2005, Vol. 204 Issue 2, p463-469. 7p. |
| Subject Terms: | *TRASTUZUMAB, *HER2 gene, *BREAST cancer, *PROTO-oncogenes, *CELLULAR pathology |
| Abstract: | Clusterin (CLU) is a heterodimeric secreted glycoprotein implicated in several physiological and pathological processes including cancer. Although recent data showed that overexpression of CLU is closely associated with disease progression in patients with breast tumor, the functional role of CLU expression in this tumor hystotype remains to be determined. The objectives in this study were to evaluate CLU expression levels after treatment with Trastuzumab, a HER2-targeted monoclonal antibody used in the clinical management of advanced breast cancer patients, and to test the usefulness of combined treatment with OGX-011, the second generation 2'-methoxyethyl gapmer oligonucleotides targeting the CLU gene, and Trastuzumab in this tumor hystotype. By using the HER-2 gene amplified-BT474 human breast cancer cells, we found Trastuzumab decreased HER-2 expression and inhibited cell proliferation without affecting apoptosis. Interestingly, Trastuzumab treatment up-regulated CLU protein expression in a dose-dependent fashion. We therefore hypothesized that the treatment with OGX-011, by blocking Trastuzumab-induced CLU expression, might potentiate the growth-inhibitory effect of Trastuzumab alone. Although OGX-011 had no effect on the behavior of the BT474 cells when used alone, it significantly enhanced the sensitivity of cells to Trastuzumab. A significant increase in the percentage of apoptotic cells, analyzed in terms of annexin V positivity and cleavage of poly(ADP-ribose) polymerase, was observed after combined treatment with OGX-011 plus Trastuzumab but not with either agent alone. Altogether our findings suggest that combined targeting of HER-2 and CLU may represent a novel, rational approach to breast cancer therapy. 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: Antisense clusterin oligodeoxynucleotides increase the response of HER-2 gene amplified breast cancer cells to Trastuzumab. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Annamaria+Biroccio%22">Annamaria Biroccio</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Carmen+D'Angelo%22">Carmen D'Angelo</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Burkhard+Jansen%22">Burkhard Jansen</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Martin+E%2E+Gleave%22">Martin E. Gleave</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Gabriella+Zupi%22">Gabriella Zupi</searchLink><relatesTo>1</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Cellular+Physiology%22">Journal of Cellular Physiology</searchLink>. Aug2005, Vol. 204 Issue 2, p463-469. 7p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22TRASTUZUMAB%22">TRASTUZUMAB</searchLink><br />*<searchLink fieldCode="DE" term="%22HER2+gene%22">HER2 gene</searchLink><br />*<searchLink fieldCode="DE" term="%22BREAST+cancer%22">BREAST cancer</searchLink><br />*<searchLink fieldCode="DE" term="%22PROTO-oncogenes%22">PROTO-oncogenes</searchLink><br />*<searchLink fieldCode="DE" term="%22CELLULAR+pathology%22">CELLULAR pathology</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Clusterin (CLU) is a heterodimeric secreted glycoprotein implicated in several physiological and pathological processes including cancer. Although recent data showed that overexpression of CLU is closely associated with disease progression in patients with breast tumor, the functional role of CLU expression in this tumor hystotype remains to be determined. The objectives in this study were to evaluate CLU expression levels after treatment with Trastuzumab, a HER2-targeted monoclonal antibody used in the clinical management of advanced breast cancer patients, and to test the usefulness of combined treatment with OGX-011, the second generation 2'-methoxyethyl gapmer oligonucleotides targeting the CLU gene, and Trastuzumab in this tumor hystotype. By using the HER-2 gene amplified-BT474 human breast cancer cells, we found Trastuzumab decreased HER-2 expression and inhibited cell proliferation without affecting apoptosis. Interestingly, Trastuzumab treatment up-regulated CLU protein expression in a dose-dependent fashion. We therefore hypothesized that the treatment with OGX-011, by blocking Trastuzumab-induced CLU expression, might potentiate the growth-inhibitory effect of Trastuzumab alone. Although OGX-011 had no effect on the behavior of the BT474 cells when used alone, it significantly enhanced the sensitivity of cells to Trastuzumab. A significant increase in the percentage of apoptotic cells, analyzed in terms of annexin V positivity and cleavage of poly(ADP-ribose) polymerase, was observed after combined treatment with OGX-011 plus Trastuzumab but not with either agent alone. Altogether our findings suggest that combined targeting of HER-2 and CLU may represent a novel, rational approach to breast cancer therapy. 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Cellular Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1002/jcp.20295 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 463 Subjects: – SubjectFull: TRASTUZUMAB Type: general – SubjectFull: HER2 gene Type: general – SubjectFull: BREAST cancer Type: general – SubjectFull: PROTO-oncogenes Type: general – SubjectFull: CELLULAR pathology Type: general Titles: – TitleFull: Antisense clusterin oligodeoxynucleotides increase the response of HER-2 gene amplified breast cancer cells to Trastuzumab. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Annamaria Biroccio – PersonEntity: Name: NameFull: Carmen D'Angelo – PersonEntity: Name: NameFull: Burkhard Jansen – PersonEntity: Name: NameFull: Martin E. Gleave – PersonEntity: Name: NameFull: Gabriella Zupi IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 08 Text: Aug2005 Type: published Y: 2005 Identifiers: – Type: issn-print Value: 00219541 Numbering: – Type: volume Value: 204 – Type: issue Value: 2 Titles: – TitleFull: Journal of Cellular Physiology Type: main |
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