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Wild-typep53 gene-induced morphological changes and growth suppression in hepatoma cells

  • Liver, Pancreas, and Biliary Tract
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Abstract

The human hepatocellular carcinoma (HCC) cell line, HLF, expresses only mutant-type p53 (mt-p53), which has an amino acid substitution at the 244th residue from glycine to alanine. HLF cells were transfected with wild-type p53 (wt-p53) cDNA construct pC53-SN3, mt-p53 cDNA construct pC53-SCX [which differs by a single nucleotide, resulting in alanine instead of valine at the 143rd residue in p53 (p53-143)], or pCMV-Neo-Bam, as a control, by a liposome method. After G418 selection, three wt-p53 stable transformants (WT), four mt-p53 transformants (MT), and three control vector transformants (VT) were obtained. We analyzed the cell growth and morphological changes of these transformants under different culture conditions [fetal calf serum (FCS), 10%, 1%, and 0%]. Whereas no difference from control in the growth rate and morphology was observed under the 10% FCS conditions, serum starvation induced remarkable phenotypical changes in all three WTs, but not in the other transformant. Corresponding to these phenotypical changes, the transcriptional activity of wt-p53 was increased more than nine fold. These results indicated that serum starvation would induce wt-p53 biological function, which is tightly linked to morphological changes and growth suppression. To induce these changes, the introduction of thewt-p53 gene itself was not sufficient, and additional triggering, i.e., serum starvation, was indispensable.

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Authors and Affiliations

  1. First Department of Internal Medicine, Yamaguchi University School of Medicine, 1144 Kogushi, 755, Ube, Yamaguchi, Japan

    Shuji Terai, Teruaki Kimura, Fumie Kurokawa & Kiwamu Okita

  2. Second Department of Biochemistry, Yamaguchi University School of Medicine, 1144 Kogushi, 755, Ube, Yamaguchi, Japan

    Takafumi Noma & Atsushi Nakazawa

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  1. Shuji Terai
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  2. Takafumi Noma
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Terai, S., Noma, T., Kimura, T. et al. Wild-typep53 gene-induced morphological changes and growth suppression in hepatoma cells. J Gastroenterol 32, 330–337 (1997). https://doi.org/10.1007/BF02934489

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  • DOI: https://doi.org/10.1007/BF02934489

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