Abstract 2436: Non canonical activation of Sonic Hedgehog pathway in uterine leiomyosarcoma

Abstract

Background: Uterine leiomyoma (ULM) and leiomyosarcoma (ULMS) are smooth muscle tumors with distinct clinical and biological behavior. They can be a cause of infertility and even death. Little is known about the factors that can to influence these tumors behavior and biology. Sonic Hedgehog (SHH) pathway components were previously implicated in the ULMS malignancy risk; however its activation mechanism is unknown. In this study, we investigated the gene expression profile of Sonic Hedgehog Signaling and pathway upstream genes in myometrium (MM), ULM and LMS cell lines. Methods: Total RNA obtained from cell lines were submitted to cDNA synthesis and quantitative real time PCR (qRT-PCR), using 7500 System (Life Technologies, USA). Gene expression of SHH, PTCH1, SMO, SUFU, GLI 1-3, CCND1, BCL-2 and BMP4 were assessed. Results: Gene expression data showed an upregulation of SMO, SUFU, GLI1, BCL-2 and BMP4 in LMS cells when compared to MM. GLI1 (RQ=11) and BCL-2 (RQ=20) genes had higher expression. In the other side, SHH, PTCH1, GLI2 and GLI3 showed upregulation in MM cells. Conclusion: Our results showed that the Sonic hedgehog pathway is activated in LMS cells but by SHH independent form (non-canonical pathway). This could be explained by the downexpression of SHH ligand and the PTCH1 receptor, and by the upexpression of SMO, GLI1 and pathway target genes as BCL-2 and BMP4 in uterine LMS cells compared to LM and MM. These results suggest a new therapeutic perspective for LMS by target drugs to inhibit SMO and GLI1 molecules. Citation Format: Natalia Garcia, Bianca C. Oliveira, Kelly P. Ferreira, Edmund C. Baracat, Katia C. Carvalho. Non canonical activation of Sonic Hedgehog pathway in uterine leiomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2436. doi:10.1158/1538-7445.AM2017-2436