Journal Article

Expression of activins C and E induces apoptosis in human and rat hepatoma cells

Susanne Vejda, Natascha Erlach, Barbara Peter, Claudia Drucker, Walter Rossmanith, Jens Pohl, Rolf Schulte-Hermann and Michael Grusch

in Carcinogenesis

Volume 24, issue 11, pages 1801-1809
Published in print November 2003 | ISSN: 0143-3334
Published online November 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg154
Expression of activins C and E induces apoptosis in human and rat hepatoma cells

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Activins C and E (homodimers of the βC and βE subunits), which are almost exclusively expressed in the liver, are members of the transforming growth factor β (TGFβ) superfamily of growth factors. We examined their expression in three different hepatoma cell lines and found that, compared with 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 activins 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 βC or βE cDNA to study the consequences of restoring activin expression in hepatoma cells. Transfection with activin βA, 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 βC or βE, as well as with activin βA, reduced the increase in cell number by up to 40% compared with 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 activins C and E share the potential to induce apoptosis in liver derived cell lines with activin A and TGFβ1.

Keywords: EGFP, enhanced green fluorescent protein; FCS, fetal calf serum; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IRES, internal ribosomal entry site; MEM, minimal essential medium; MTT, methylthiazoltetrazolium; MTX, methotrexate; PBS, phosphate-buffered saline; RPL6, ribosomal protein L6; TGFβ, transforming growth factor β

Journal Article.  6339 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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