Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer |
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Authors: | Woo Ho-Hyung Yi Xiaofang Lamb Tiffany Menzl Ina Baker Terri Shapiro David J Chambers Setsuko K |
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Affiliation: | Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA. hwoo@azcc.arizona.edu |
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Abstract: | cis-acting elements found in 3'-untranslated regions (UTRs) are regulatory signals determining mRNA stability and translational efficiency. By binding a novel non-AU-rich 69-nucleotide (nt) c-fms 3' UTR sequence, we previously identified HuR as a promoter of c-fms proto-oncogene mRNA. We now identify the 69-nt c-fms mRNA 3' UTR sequence as a cellular vigilin target through which vigilin inhibits the expression of c-fms mRNA and protein. Altering association of either vigilin or HuR with c-fms mRNA in vivo reciprocally affected mRNA association with the other protein. Mechanistic studies show that vigilin decreased c-fms mRNA stability. Furthermore, vigilin inhibited c-fms translation. Vigilin suppresses while HuR encourages cellular motility and invasion of breast cancer cells. In summary, we identified a competition for binding the 69-nt sequence, through which vigilin and HuR exert opposing effects on c-fms expression, suggesting a role for vigilin in suppression of breast cancer progression. |
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