Evidence of functional distinction between WNT5A Isoform A and Isoform B in osteosarcoma cells

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Oluwole O. Akindahunsi (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Karen Katula

Abstract: WNT5A is a secreted ligand involved in differentiation, proliferation, cell movement, and apoptosis. Various studies have shown WNT5A misregulation in cancer and that it can act as both a tumor suppressor, and oncogene. The WNT5A gene has two transcription sites, producing mRNA transcripts that code for unique protein isoforms, termed Isoform A and Isoform B in this lab. In a recent study, Isoforms A and B were found to differentially effect proliferation, indicating the isoforms are functionally distinct. The focus of this study was on the functional distinctions between the WNT5A Isoform A and Isoform B in the osteosarcoma cell line SaOS-2. In osteosarcoma, levels of Isoform A expression are higher than normal in normal osteoblast, whereas Isoform B expression is nonexistent, indicating it is functioning as a tumor suppressor. Stable lines of SaOS-2 were generated expressing Isoform B, overexpressing Isoform A and expressing GFP, as a control. The cell lines were confirmed to expresses the expected isoform mRNA at higher levels than that of the control and to have correspondingly higher levels of WNT5A protein. These cell lines were used in assays for proliferation, migration, invasion, and apoptosis. Results show that Isoform A overexpression stimulates migration and apoptosis resistance, whereas increased Isoform B had no effect. This indicates that Isoform A and Isoform B each stimulate separate non-canonical WNT signaling pathways independent from one another. Increased Isoform B expression slightly inhibited invasiveness, but the results are still inconclusive. Both Isoform A and Isoform B both had no effect on proliferation, relative to the GFP control. Overall, these results suggest that Isoform A and Isoform B are functionally distinct, and that the two different isoforms activate different non-canonical pathways.

Additional Information

Language: English
Date: 2014
Cancer, Isoform A, Isoform B, SAOS-2, WTN5A
Wnt proteins

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