Abstract
Abstract Purpose: Currently, there is no effective chemotherapy for the treatment of hepatocellular carcinoma (HCC). Both HCC and hepatoblastoma (HB) remain lethal in their metastatic forms. Therefore, understanding the molecular mechanisms of tumor survival and proliferation is critical for developing novel therapies. Our lab has shown that YAP, a transcription factor, is involved in liver regeneration. Specifically, increases in nuclear YAP have been coupled with expression of genes important for cell proliferation. We therefore sought to examine whether there is increased nuclear localization of YAP in liver tumors. Methods: Tumor tissue and normal liver tissue from 3 pediatric patients with HCC (all males, mean age 10.63 years), and 6 HB patients (4 males and 2 females, mean age 2.99 years) were stained for YAP using immunohistochemistry. Multiple high-power fields were photographed for each sample. Using ImageJ software, the number of YAP-positive nuclei were counted and expressed as a mean percentage of total nuclei. Results: The percentage of nuclei staining positive for YAP was increased in tumor cells compared to normal liver in 3/3 of the HCC tumors. In addition, YAP nuclear staining was significantly increased in 2/6 of the HB tumors. Conclusion: All HCC tumors and 33% of the HB showed an increase in the nuclear localization of transcription factor YAP. The increased activity of YAP in the nuclei of tumor cells may indicate a crucial role for YAP in tumor proliferation and survival. Targeting YAP or its upstream pathway (Hippo) may provide a novel target for therapy. Citation Format: Michael J. LaQuaglia, James Grijalva, Kaly Mueller, Antonio Perez-Atayde, Heung Bae Kim, Ghazaleh Sadri-Vakili, Khashayar Vakili. YAP protein expression and subcellular localization in pediatric liver tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2107. doi:10.1158/1538-7445.AM2015-2107
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