Carcinogenesis Advance Access published online on August 29, 2003
Carcinogenesis, doi:10.1093/carcin/bgg154
© 2003 by Oxford University Press
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CARCINOGENESIS
1 Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria
* Corresponding author. E-mail: michael.grusch{at}univie.ac.at.
Received 15 January 2003
; revised 12 August 2003
; accepted 14 August 2003
Activin C and E (homodimers of
Expression of activin C and E induces apoptosis in human and rat hepatoma cells
2 BIOPHARM Gmbh, Czernyring 22, D-69115 Heidelberg, Germany
C and
E subunits), which are almost exclusively expressed in the liver, are members of the transforming growth factor
(TGF
) superfamily of growth factors. We examined their expression in three different hepatoma cell lines, and found that, compared to normal liver or primary hepatocytes, human hepatoblastoma (HepG2), human hepatocellular carcinoma (Hep3B) and rat hepatoma (H4IIEC3) cells have either completely lost or drastically reduced the expression of activin C and E. In order to elucidate the biological function of these proteins we transiently transfected HepG2, Hep3B and H4IIEC3 cell lines with rat activin
C, or
E cDNA to study the consequences of restoring activin expression in hepatoma cells. Transfection with activin
A, a known inhibitor of hepatic DNA synthesis and inducer of apoptosis, served as a positive control. We found that transfection of the three cell lines with activin
C, or
E, as well as with activin
A, delayed the increase of cell number by up to 40% compared to cells transfected with a control plasmid. Co-culture with a CHO cell clone secreting activin C also inhibited HepG2 cell multiplication. Furthermore, the three hepatoma cell lines studied showed an enhanced rate of apoptosis and elevated levels of active caspases in response to activin transfection. These results indicate that activin C and E share the potential to induce apoptosis in liver derived cell lines with activin A and TGF
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