Interferon regulatory factor-1 (IRF-1) is a master regulator of IFN-gamma induced gene transcription. Previously we have shown that IRF-1 transcriptionally induces CEACAM1 via an ISRE (Interferon-Stimulated Response Element) in its promoter.
CEACAM1 pre-mRNA undergoes extensive alternative splicing (AS) generating isoforms to produce either a short (S) cytoplasmic domain expressed primarily in epithelial cells or as an ITIM-containing long (L) isoform in immune cells.
Methods:
The transcriptional and molecular mechanism of CEACAM1 minigenes AS containing promoter ISREs mutations in the breast epithelial, MDA-MB-468, cell line was detected using flow cytometry. In addition, transcriptome sequencing was utilized to determine whether IRF-1 could direct the AS of other genes as well.
Tumor xenografts were used to evaluate CEACAM1 isoform expression on the leading edge of breast tumor cells.
Results:
In the present study, we provide evidence that CEACAM1?s promoter and variable exon 7 cross-talk allowing IRF-1 to direct AS events. Transcriptome sequencing shows that IRF-1 can also induce the global AS of genes involved in regulation of growth and differentiation as well as genes of the cytokine family.
Furthermore, MDA-MB-468 cells grown as tumor xenografts exhibit an AS switch to the L-isoform of CEACAM1, demonstrating that an in vivo inflammatory milieu is also capable of generating the AS switch, similar to that found in human breast cancers [1].
Conclusions:
The novel AS regulatory activities attributed to IRF-1 indicate that the IFN-gamma response involves a global change in both gene transcription and AS in breast epithelial cells.
Author: Kenneth J DeryMaciej KujawskiXiwei WuTung NgyuenJohn H YimJohn E Shively
Credits/Source: Molecular Cancer 2014, 13:64
Published on: 2014-03-21
Tweet
News Provider: 7thSpace Interactive
Social Bookmarking
RETWEET This! | Digg this! | Post to del.icio.us | Post to Furl | Add to Netscape | Add to Yahoo! | Rojo
There are no comments available. Be the first to write a comment.