Abstract 275: Burkitt lymphoma cells express GLI1 but are not responsive to Hedgehog signaling

Abstract

Abstract Activation of the Hedgehog (HH) signaling pathway has been associated with a wide variety of human cancers. Some B-cell lymphomas express components of the HH signaling pathway, including patched (PTCH), smoothened (SMO), and GLI1. There is also evidence that HH ligands function as survival factors in these malignancies. However, specific roles for HH signaling in Burkitt lymphoma have not been characterized. Previously we showed that constitutive expression of c-MYC in Burkitt lymphoma cells up-regulates GLI1 and that GLI1 functions as an anti-apoptotic factor in this setting. Similar to other B-cell malignancies, we have shown expression of PTCH, SMO, and GLI1 in five Burkitt lymphoma cells lines. To test the role of HH signaling in Burkitt lymphoma, we exposed the cells to Sonic Hedgehog peptide or to SHH-containing conditioned media and measured the level of PTCH and GLI1 mRNA expression by quantitative RT PCR; cell viability by MTT assay; cell proliferation by BrdU incorporation; and apoptosis by caspase 3/7 assay. Although control cells (MC3T3) showed dramatic up-regulation of GLI1 and PTCH expression, the Burkitt lymphoma cell lines did not show changes in any of the assays. To inhibit HH signaling, we treated the Burkitt lymphoma cells with the SMO inhibitor, cyclopamine. Cyclopamine treatment did not affect GLI1 expression measured by quantitative RT PCR. Cyclopamine reduced viability of Burkitt lymphoma cells measured by MTT assays only when used at high concentrations (>5 µm), possibly representing a non-specific cytotoxic effect. Collectively, the results suggest that Burkitt lymphoma cells are not HH responsive and that constitutive c-MYC expression plays an important role in regulating GLI1 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 275. doi:10.1158/1538-7445.AM2011-275