Genistein Affects HER2 Protein Concentration, Activation and Promoter Regulation via Estrogen Receptor-and non-Estrogen Receptor-Mediated Mechanisms
Genistein Affects HER2 Protein Concentration, Activation and Promoter Regulation via Estrogen Receptor-and non-Estrogen Receptor-Mediated Mechanisms
| dc.contributor.author | Sakla, Mary | |
| dc.contributor.author | MacDonald, Ruth | |
| dc.contributor.author | Ansell, Pete | |
| dc.contributor.author | Shenouda, Nader | |
| dc.contributor.author | Lubahn, Dennis | |
| dc.contributor.author | MacDonald, Ruth | |
| dc.contributor.department | Food Science and Human Nutrition | |
| dc.date | 2018-02-15T03:18:47.000 | |
| dc.date.accessioned | 2020-06-30T03:59:49Z | |
| dc.date.available | 2020-06-30T03:59:49Z | |
| dc.date.copyright | Mon Jan 01 00:00:00 UTC 2007 | |
| dc.date.embargo | 2014-01-11 | |
| dc.date.issued | 2007-10-02 | |
| dc.description.abstract | <p>The <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> proto-oncogene, a member of the epidermal growth factor receptor family, is overexpressed in 20–30% of breast cancers. <a href="http://link.springer.com/search?dc.title=Genistein&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">Genistein</a>, the main soy isoflavone, interacts with estrogen receptors (ER) and it is also a potent tyrosine kinase inhibitor. Previously, our laboratory found that genistein delayed mammary tumor onset in transgenic mice that overexpress <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> gene. Our goal was to define the mechanism through which genistein affects mammary tumorigenesis in<em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> overexpressing mice. We hypothesized that genistein inhibits <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> activation and expression through ER-dependent and ER-independent mechanisms. <a href="http://link.springer.com/search?dc.title=Genistein&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">Genistein</a> inhibited total <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> protein expression and tyrosine phosphorylation in BT-474, an ERα (−) and ERβ (+) human breast cancer cell line, however, E2 had no effect. Taken together, these data suggest that genistein has an ER-independent inhibitory effect, presumably, through tyrosine kinase inhibition activity. <a href="http://link.springer.com/search?dc.title=Genistein&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">Genistein</a> at 1.0 μM mimicked E2 and down-regulated <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> protein phosphorylation when BT-474 was co-transfected with ERα, but not ERβ. Although E2 and overexpression of <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> can promote mammary tumorigenesis, an inverse relationship between ER expression and <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> overexpression has been found in human breast cancer. We cloned a 500-bp promoter region upstream of the<em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> transcription initiation site. Co-transfection with ERα, but not with ERβ, down-regulated <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em>promoter reporter in BT-474. At concentrations ≥1 μM, genistein inhibited <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> promoter reporter in the absence of ERα. In conclusion, genistein at ≥1 μM inhibited <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> protein expression, phosphorylation, and promoter activity through an ER-independent mechanism. In the presence of ERα, genistein mimicked E2 and inhibited <em><a href="http://link.springer.com/search?dc.title=HER2&facet-content-type=ReferenceWorkEntry&sortOrder=relevance">HER2</a></em> protein phosphorylation. These data support genistein’s chemo-prevention and potential chemo-therapeutic roles in breast cancer.</p> | |
| dc.description.comments | <p>This is a manuscript of an article from Endocrine 32 (2007): 69. doi: <a href="http://www.dx.doi.org/10.1007/s12020-007-9006-1" target="_blank">10.1007/s12020-007-9006-1</a>. Posted with permission. "The Original Publication is Available at www.springerlink.com"</p> | |
| dc.format.mimetype | application/pdf | |
| dc.identifier | archive/lib.dr.iastate.edu/fshn_ag_pubs/78/ | |
| dc.identifier.articleid | 1075 | |
| dc.identifier.contextkey | 6267546 | |
| dc.identifier.s3bucket | isulib-bepress-aws-west | |
| dc.identifier.submissionpath | fshn_ag_pubs/78 | |
| dc.identifier.uri | https://dr.lib.iastate.edu/handle/20.500.12876/37591 | |
| dc.language.iso | en | |
| dc.source.bitstream | archive/lib.dr.iastate.edu/fshn_ag_pubs/78/2007_MacDonaldRS_GenisteinAffectsHER.pdf|||Sat Jan 15 01:53:58 UTC 2022 | |
| dc.source.uri | 10.1007/s12020-007-9006-1 | |
| dc.subject.disciplines | Cancer Biology | |
| dc.subject.disciplines | Food Science | |
| dc.subject.disciplines | Human and Clinical Nutrition | |
| dc.subject.disciplines | Women's Health | |
| dc.subject.keywords | Genistein | |
| dc.subject.keywords | HER2 | |
| dc.subject.keywords | er | |
| dc.subject.keywords | Breast Cancer | |
| dc.title | Genistein Affects HER2 Protein Concentration, Activation and Promoter Regulation via Estrogen Receptor-and non-Estrogen Receptor-Mediated Mechanisms | |
| dc.type | article | |
| dc.type.genre | article | |
| dspace.entity.type | Publication | |
| relation.isAuthorOfPublication | bfbd6b6b-8feb-40d3-8ccb-42c0d0b238d7 | |
| relation.isOrgUnitOfPublication | 4b6428c6-1fda-4a40-b375-456d49d2fb80 |
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