ErbB family expression in osteosarcoma
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Abstract
Osteosarcoma (OS) is the most common bone malignancy among children and teenagers. Currently the gold standard treatment is surgery and chemotherapy; however the 5 year survival for these patients remains 60 to 70%. There has being tremendous interest in identifying markers of prognostic and therapeutic significance being a possible target the ErbB family of protein receptor tyrosine kinases (RYT). There are four members in the ErbB family, three (EGFR, Her2 and Her4) of which are expressed in primary OS cell lines. In this study we investigated the contributions of each of ErbB RYT to OS pathogenesis using cells genetically modified to knock-down the expression of either EGFR or Her-4. Cells were tweaked with ligands that target either EGFR (EGF) or Her-4 (heregulin, NRG1) to see which Ph ErbB-family member residues are activated, changed, or reduced. Expression of Ph EGFR was reduced in OS-O 3696 and Saos-2 3696 when compared to OS-O NC and Saos-2 NC. When stimulated with EGF, expression of Ph Her-2 decreased in OS-D 3696 when compared with parental D and OS-D NC; expression was reduced in Saos-2 3696 compared to Saos-2 NC. Expression of Ph Her-4 Ph was slightly increased in Saos-2 3696 compared with Saos-2 NC. We saw a slightly decrease in the expression of Ph EGFR and Ph Her-4 when stimulated with EGF in OS-D 1608 compared to OS-D NC. Moreover in OS-D 3847, the expression of both Ph EGFR and Ph Her-4 was significantly decreased while full length Her-4 expression was reduced in OS-D 3847 compared to OS-D 1608 and OS-D NC.
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This presentation is supported by the National Cancer Institute through the U54 CA096297/CA096300: UPR/MDACC Partnership for Excellence in Cancer Research Training Program.
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