Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentAbstract # 67Amal M.El-Naggar 1,2 , Cristina Tognon 2 , Fan Zhang 2 , Joan Mathers 2 , and Poul HB.Sorensen 1,21Pathology and Laboratory Medicine Department, UBC, 2 Molecular OncologyDepartment, BCCRCAmal Mohammad El-Naggary box binding protein-1 is a major contributor tosarcoma cells motility and aggressivenessBackround/ObjectivesObjectives: 1- Evaluating the effect of YB-1 knock down on sarcoma cells motility (invasion/migration). 2- Detectingthe possible relationship between YB-1 and a common marker featuring aggressiveness, hypoxia inducible factor-1alpha (HIF-1α).Background: Sarcoma are diverse group of malignant neoplasms of mesenchymal origin, commonly affecting pediatricage group and are, unfortunately, characterized by early metastatic spread, aggressive behavior and poor prognosis.Genetic alterations play an important role in sarcoma etiology. One of the genes recently believed to play a role insarcoma is Y-box binding protein-1 (YB-1). Y-box binding protein-1 (YB-1) is a member of highly conservative familyof proteins which can bind single and double stranded DNA and single stranded RNA so executing a control overboth transcription and translation of multitude of genes. Numerous studies pointed to the essential role of YB-1 innormal development as well as in malignant transformation. One of the well studied models demonstrating the role ofYB-1 in carcinogenesis is breast cancer. In this model, it was shown that YB-1 promotes the epithelial-mesenchymaltransition (EMT) and hence conferring the malignant cells with the aggressive features. However, very few studieshave specifically investigated the role of YB-1 in sarcoma.MethodsTC32, MG63 and RH30, representing Ewing Family Tumor (EFT), osteosarcoma (OS) and rhabdomyosarcoma(RMS), respectively were selected for the current study. The cells were treated with siCTRL or siYB-1 siRNA froma smart pool. Sarcoma Cell motility was assessed using wound healing assay and Boyden chamber migration assay.YB-1- HIF-1α relationship was assessed using hypoxia chamber incubation, immunoblotting, polysomal fractionationand real-time RT-PCR.ResultsInterference with YB-1 expression using siRNA from smart pool lead to marked reduction of sarcoma cells motility(Invasion/Migration). Another interesting finding is the intimate relation between YB-1-hypoxia- and HIF-1α.We found that, both of YB-1 and HIF-1α are induced under hypoxia. Using polysomal fractionation and qPCR,we found that YB-1 is a major translational regulator of HIF-1α. These findings may explain the role of YB-1 inpromoting the aggressiveness of sarcoma cells.Conclusion1-YB-1 strongly promotes the migration and invasion of sarcoma cells. 2- YB-1 is a major regulator of HIF-1α. 3- Bothof YB-1 and HIF-1α are upregulated by hypoxia. 4- YB-1 is very likely a step forward in understanding the aggressivenature of sarcoma and may represent a promising future target in treatment of this type of malignancies.78 2 0 1 0 * P o s t e r P r e s e n t a t i o n s