College of Agriculture & Natural Resources

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Subject: search.filters.subject.Apoptosis

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    THE POTENTIAL DICHOTOMOUS ROLE OF ACTIVATING TRANSCRIPTION FACTOR 3 (ATF3) IN COLON CANCER
    (2015) Jiang, Xiaojing; Lee, Seong-Ho; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Colorectal 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.
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    FUNCTIONAL CHARACTERIZATION OF THE VIRAL FLICE INHIBITORY PROTEIN OF RHESUS MONKEY RHADINOVIRUS
    (2011) Ritthipichai, Krit; Zhang, Yanjin; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Rhesus monkey rhadinovirus (RRV) is a gamma-2 herpesvirus closely related to Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is associated with several malignant diseases, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. Here we found that RRV viral FLICE inhibitory protein (vFLIP) inhibits apoptosis. In HeLa cells with vFLIP expression, cleavage of poly [ADP-ribose] polymerase 1 (PARP-1) and activities of caspase 3, 7, and 9 were much lower than controls. RRV vFLIP was able to enhance cell survival under starved condition or apoptosis induction. After apoptosis induction, autophagosome formation was enhanced in cells with vFLIP expression and when autophagy was inhibited, these cells underwent apoptosis. Moreover, RRV latent infection of BJAB B-lymphoblastoid cells protects the cells against apoptosis. Knockdown of vFLIP expression in the RRV-infected BJAB cells with siRNA abolished the protection against apoptosis. These findings indicate that RRV vFLIP protects cells against apoptosis by enhancing autophagosome formation.