Z Gastroenterol 2012; 50 - P5_10
DOI: 10.1055/s-0031-1295966

The protein phosphatase 2A inhibitior I–2PP2A/SET is highly expressed during murine fetal liver development and hepatocarcinogenesis

HM Curth 1, S Schievenbusch 1, J Marquardt 1, G Pryymachuk 1, T Goeser 1, D Nierhoff 1
  • 1Department of Gastroenterology and Hepatology, Köln

Over the recent years, substantial progress in identification and characterisation of fetal liver stem/progenitor cells (FLSPC) as a resource for regenerative medicine has been made. Because of their high repopulation potential, there is great interest to elucidate the mechanisms involved in FLSPC proliferation and differentiation. Therefore, we analyzed differences in protein expression patterns of purified FL 13,5 FLSPC versus adult liver (AL) by 2D-gelelectrophoresis and subsequent mass spectrometry. We identified several proteins predominantly expressed in FLSPC. Among these, Protein SET (I–2PP2A/SET), an inhibitor of protein phosphatase 2A tumor suppressor1, was highly expressed during early stages of mouse liver development. In chronic leukaemia, increased levels of I–2P P2A/SET correlated significantly with disease severity and overall survival2, so we further investigated a potential relevance of I–2PP2A/SET expression for hepatocarcinogenesis using murine hepatoma cell lines and Cre-inducible SV40 T-antigen transgenic mice (Alb-SV40TAgind). I–2PP2A/SET was abundantly detectable in Hepa 1–6 and Hepa 129 mouse hepatoma cell lines compared to normal liver. More interestingly, expression-levels of I–2PP2A/SET continuously increased during different stages of HCC-development indicating a potential role for malignant transformation. Together, our findings suggest that I–2PP2A/SET is an oncofetal protein significantly associated with FLSPC activation and during the progression of liver cancer. Further studies will focus on the functional role of this protein for these two processes.

Literatur: 1. Li M, Makkinje A, Damuni Z. The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A. J Biol Chem. 1996;271(19):11059-62. 2. Christensen DJ, Chen Y, Oddo J, et al. SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin's lymphoma: a predictor of aggressive disease and new treatment target. Blood. 2011 [Epub ahead of print]

HCC - liver stem/progenitor cells - protein phosphatase 2A