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Ai, Lingbao; Kim, Wan-Ju; Alpay, Merve; Tang, Ming; Pardo, Carolina E.; Hatakeyama, Shigetsugu; May, W. Stratford; Kladde, Michael P.; Heldermon, Coy D.; Siegel, Erin M.; Brown, Kevin D.
<?xml version='1.0' encoding='utf-8'?> <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> <dc:creator>Ai, Lingbao</dc:creator> <dc:creator>Kim, Wan-Ju</dc:creator> <dc:creator>Alpay, Merve</dc:creator> <dc:creator>Tang, Ming</dc:creator> <dc:creator>Pardo, Carolina E.</dc:creator> <dc:creator>Hatakeyama, Shigetsugu</dc:creator> <dc:creator>May, W. Stratford</dc:creator> <dc:creator>Kladde, Michael P.</dc:creator> <dc:creator>Heldermon, Coy D.</dc:creator> <dc:creator>Siegel, Erin M.</dc:creator> <dc:creator>Brown, Kevin D.</dc:creator> <dc:date>2014-01-01</dc:date> <dc:description>TRIM29 (ATDC) exhibits a contextual function in cancer, but seems to exert a tumor-suppressor role in breast cancer. Here, we show that TRIM29 is often silenced in primary breast tumors and cultured tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial-mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene-expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival, increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT. (C) 2014 AACR.</dc:description> <dc:identifier>https://aperta.ulakbim.gov.trrecord/63399</dc:identifier> <dc:identifier>oai:zenodo.org:63399</dc:identifier> <dc:rights>info:eu-repo/semantics/openAccess</dc:rights> <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights> <dc:source>CANCER RESEARCH 74(17) 4875-4887</dc:source> <dc:title>TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior</dc:title> <dc:type>info:eu-repo/semantics/article</dc:type> <dc:type>publication-article</dc:type> </oai_dc:dc>
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