期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 276, 期 2, 页码 466-471出版社
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.3512
关键词
TRAIL; TNF family; IFN-gamma; human colon cancers; Caco-2; HT29
资金
- NIA NIH HHS [R01 AG10885] Funding Source: Medline
- NIDDK NIH HHS [P01 DK35608, R01 DK48498] Funding Source: Medline
TRAIL, a novel member of the TNF family, acts through membrane receptors to induce apoptosis of activated T lymphocytes and may represent a mechanism for the immune escape of certain cancers. Various cytokines appear to increase expression of other TNF family members; however, the regulation of TRAIL has not been defined. The purpose of this study was to assess molecular mechanisms regulating TRAIL gene expression in human colon cancers. In this study, we have cloned the human TRAIL (hTRAIL) promoter (similar to 1.6 kb) and identified a number of putative transcription factor binding sites such as NFAT, AP-1 and Spl sequences which are important for the expression of other TNF family members. Transient transfections of 5'-deletion promoter constructs into either Caco-2 or HT29 colon cancer cells identified TRAIL promoter regions critical for both basal and interferon-gamma (IFN-gamma)-mediated induction. Furthermore, induction of TRAIL mRNA levels was demonstrated in HT29 and Caco-2 cells with IFN-gamma treatment suggesting an important role for this cytokine in TRAIL expression. (C) 2000 Academic Press.
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