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EP254/#645  The BCAM-AKT2 fusion protein effect on the IGF1 signaling pathway in epithelial ovarian cancer cells
  1. Hala Khazem1,
  2. Ilan Bruchim1,
  3. Shilhav Meisel-Sharon1,
  4. Shay Hantisteanu2,
  5. Mordechai Hallak2 and
  6. Haim Werner3
  1. 1Technion, Faculty of Medicine, Bat Galim, Israel
  2. 2Hillel Yaffe Medical Center, Obstetrics and Gynecology, Hadera, Israel
  3. 3Tel Aviv University, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv, Israel


Introduction The Insulin Growth Factor1 Receptor (IGF1R) has been identified as a key player in the development of ovarian cancer, making it an appealing target for therapeutic intervention. Fusion genes associated with the IGF1R are good candidates to play this role. Recently, the BCAM-AKT2 fusion protein was identified in ovarian cancer patients. We aim to investigate the BCAM-AKT2 fusion protein involvement in the IGF1 signaling pathway and the mechanism behind the oncogenic effect in epithelial ovarian cancer (EOC).

Methods In-vitro experiments were conducted in EOC cell lines. Protein expression levels of BCAM-AKT2, IGF1R, and the downstream key factors were measured by western blots. In addition, an XTT assay was used to measure the effect of the BCAM-AKT2 fusion protein on proliferation of EOC cell line. Moreover, RNA from SKOV3 and OVCAR4 transfected cells was extracted and RNA-seq was performed to determine the effect of BCAM-AKT2 on gene expression.

Results XTT assays suggest that BCAM-AKT2 induces EOC proliferation. RNA-seq experiment revealed activation of unfolded protein response, and inhibition of viral response, interferon and pyroptosis signaling pathways as a result of BCAM-AKT2 overexpression in SKOV3. However, BCAM-AKT2 did not affect gene expression in OVCAR4. Interestingly, IGF1R protein expression and activation were not affected by the BCAM-AKT2 expression. Moreover, BCAM-AKT2 phosphorylation is independent of IGF1 treatment.

Conclusion/Implications Our results suggest a possible effect of the BCAM-AKT2 fusion protein on key canonical pathways in EOC. We believe that elucidation of the mechanism of the fusion protein will help identify new biomarkers for ovarian cancer.

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