Regulation of Trail Receptor Expression in Human Melanoma View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2005

AUTHORS

Peter Hersey , Si Yi Zhang , Xu Dong Zhang

ABSTRACT

In previous studies we have shown that the level of expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor R2 was a major determinant of the sensitivity of melanoma cell lines to TRAIL-induced apoptosis. Transcriptional events regulating TRAIL death receptor expression have been the focus of much study, but our investigations point to a more important role for posttranscriptional events in regulation of TRAIL death receptors. First, although there was a wide variation in TRAIL-R2 expression between melanoma cell lines, this did not correlate with mRNA expression assessed by real-time PCR. Similarly, early passage primary cultures from patients tended to have low TRAIL-R2 protein expression compared to cells in later passage cultures, even though TRAIL-R2 mRNA expression was similar in early and late passages. Second, generation of TRAIL-resistant melanoma lines by culture in TRAIL was also associated with decreased expression of TRAIL-R2 protein, but TRAIL-R2 mRNA levels were similar to those in parental high-TRAIL-R2 expressing cells. The latter model was used to explore post-transcriptional regulation of TRAIL-R2. Expression from a luciferase reporter gene construct with the 3′ untranslated region (UTR) (but not the 5′ UTR) of TRAIL-R2 was suppressed when transfected into the TRAIL-selected (resistant) melanoma lines and in early passage (resistant) primary melanoma cultures. RNA gel shift assays demonstrated protein(s) binding to the 3′UTR but not the 5′UTR of TRAIL-R2 mRNA. These results suggest that TRAIL-R2 expression in melanoma cell lines is determined in large part by posttranscriptional events and that protein(s) binding to the 3′UTR region of TRAIL-R2 mRNA may play a key role in this regulation. Decoy receptors appeared to play little or no role in regulation of TRAIL-mediated apoptosis of melanoma. More... »

PAGES

175-187

Identifiers

URI

http://scigraph.springernature.com/pub.10.1385/1-59259-851-x:175

DOI

http://dx.doi.org/10.1385/1-59259-851-x:175

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006126383


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