THE POTENTIAL DICHOTOMOUS ROLE OF ACTIVATING TRANSCRIPTION FACTOR 3 (ATF3) IN COLON CANCER

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dc.contributor.advisorLee, Seong-Hoen_US
dc.contributor.authorJiang, Xiaojingen_US
dc.contributor.departmentNutritionen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2016-02-09T06:36:10Z
dc.date.available2016-02-09T06:36:10Z
dc.date.issued2015en_US
dc.description.abstractColorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. During the tumorigenesis and metastasis of CRC, cells encounter numerous cellular and molecular events. ATF3, a member of the ATF/CREB transcription factor family, plays an important role on regulation of apoptosis and is regarded as a potential molecular target for chemoprevention and chemotherapy of colon cancer. The current study was performed to investigate cellular and molecular mechanisms by which ATF3 affects colon cancer-related phenotypes including apoptosis and metastasis. Here, we demonstrated that knockdown of ATF3 using small interfering RNA (siRNA) promotes the expression of anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2), in colon cancer cells, while overexpression of ATF3 resulted in a dramatic decrease in Bcl-2 protein. Gain of function of ATF3 in colon cancer cell line HCT116 led to an increase of pro-apoptotic protein Bcl-2 homologous antagonist killer (Bak), followed by the induction of apoptosis. Furthermore, we observed that ATF3 overexpression downregulated expression of epithelial-mesenchymal transition (EMT)-related transcription factors. However, mammosphere forming assay indicated that ATF3 overexpressed colon cancer cells form larger and more budding sites compared to control, which is associated with an increase of cluster of differentiation 44 (CD44) expression and a decrease of retinoblastoma (Rb) and tight junction protein zonula occludens (ZO)-1. This study suggested that ATF3 may play a dichotomous role in regulation of apoptosis and metastasis in colon cancer.en_US
dc.identifierhttps://doi.org/10.13016/M2BX4K
dc.identifier.urihttp://hdl.handle.net/1903/17382
dc.language.isoenen_US
dc.subject.pqcontrolledNutritionen_US
dc.subject.pquncontrolledApoptosisen_US
dc.subject.pquncontrolledATF3en_US
dc.subject.pquncontrolledBcl-2en_US
dc.subject.pquncontrolledEMTen_US
dc.subject.pquncontrolledGene overexpressionen_US
dc.subject.pquncontrolledMetastasisen_US
dc.titleTHE POTENTIAL DICHOTOMOUS ROLE OF ACTIVATING TRANSCRIPTION FACTOR 3 (ATF3) IN COLON CANCERen_US
dc.typeThesisen_US

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