ABL1 is Overexpressed and Activated in Hepatocellular Carcinoma
Lennox Chitsike
Department of Surgery, Oncology Institute, Loyola University Chicago Stritch School of Medicine, 2160 South 1st Avenue., Maywood, IL 60153, USA
Xianzhong Ding
Department of Pathology, Loyola University Chicago Stritch School of Medicine, 2160 South 1st Avenue., Maywood, IL 60153, USA
Peter Breslin
Department of Molecular and Cellular Physiology, Loyola University Chicago Stritch School of Medicine, 2160 South 1st Avenue., Maywood, IL 60153, USA
Wei Qiu *
Department of Surgery, Oncology Institute, Loyola University Chicago Stritch School of Medicine, 2160 South 1st Avenue., Maywood, IL 60153, USA
*Author to whom correspondence should be addressed.
Abstract
Background and Aims: ABL1 is a non-receptor tyrosine kinase of the Abelson (Abl) family, which plays an important role in cell growth, survival, invasiveness, adhesion, and migration. Despite the well-known role of BCR-ABL in hematologic malignancies, the role of ABL1 in hepatocarcinogenesis remains unknown. In this study, we want to determine if ABL1 is dysregulated in HCC.
Methods: We analyzed ABL1 mRNA in two cohorts of HCC databases from Oncomine. In addition, we performed immunohistochemistry (IHC) to examine the expression of ABL1 and p-ABL1 (Y412) in HCC tissue microarray (TMA). Further, we examined ABL1 expression and activity in oncogenes cMET/β-catenin-induced mouse HCC model.
Results: We found that ABL1 mRNA is overexpressed in over 50% of HCC. We also found that ABL1 protein expression is upregulated or activated in about 35% HCC specimens compared to adjacent normal liver. In addition, we found that ABL1 protein expression is upregulated and activated in cMET/β-catenin-induced HCC.
Conclusion: ABL1 is overexpressed and activated in human and mouse HCC. ABL1 might be a potential therapeutic target for HCC.
Keywords: ABL1, hepatocellular carcinoma, MET/CAT, CRKL