Tumorigenesis is a complex process that begins with the accumulation of several aberrant gene mutations that often favor cell proliferation while antagonizing anti-proliferative signaling pathways. Tumor cells acquire additional genetic alterations, which allow them to change their cellular metabolism, promote angiogenesis, invade tissue, and metastasize. Together, the genetic changes that abrogate the function of tumor suppressors and promote oncogenesis are key to cellular transformation and tumorigenesis. A novel Ig domain-containing adhesion molecule (Ig-CAM), Transmembrane and Immunoglobulin (Ig) Domain-containing 1 (TMIGD1), was recently identified in our laboratory. TMIGD1 is expressed in renal epithelial cells and plays a protective role against oxidative cell injury. TMIGD1 expression is downregulated in human renal cancers. However, the mechanisms of downregulation of TMIGD1 in renal cancer have yet to be defined.
In this study, we investigated the transcriptional regulation of TMIGD1 using a green fluorescent protein (GFP) reporter assay. The proximal promoter of human TMIGD1 contains multiple CCAAT box sequences with the GGCCAATCT consensus, which are putative binding sites for the transcription factor CCAAT/Enhancer-binding protein (C/EBPβ). This study demonstrates that the transcriptionally active C/EBPβ/LAP activates the TMIGD1 promoter, while the transcriptionally inactive C/EBPβ/LIP inhibits TMIGD1 promoter activity. When the putative CCAAT box sequences are deleted from the TMIGD1 promoter, C/EBPβ/LAP no longer has a marked effect on the promoter activity. Through additional analysis, we show that several transcription factors and proteins that are commonly implicated in renal cancers, including pVHL, HIF1α, HIF2α, β-catenin, and APC, do not seem to have a noticeable effect on TMIGD1 promoter activity. Collectively, the present study identifies C/EBPβ as an important transcription factor in the transcriptional regulation of TMIGD1. Furthermore, the study suggests a possible role for C/EBPβ in downregulation of TMIGD1 in renal cancer. / 2018-07-11T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/23711 |
| Date | 11 July 2017 |
| Creators | Ali, Marwa |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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