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Function of 90-kDa heat shock protein in cellular differentiation of human embryonal carcinoma cells

  • Growth, Differentiation and Senescence
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Summary

Heat shock proteins (HSPs) have been recognized as molecules that maintain cellular homeostasis during changes in the environment. Here we report that HSP90 functions not only in stress responses but also in certain aspects of cellular differentiation. We found that HSP90 slowed remarkably high expression in undifferentiated human embryonal carcinoma (EC) cells, which were subsequently dramatically down-regulated during in vitro cellular differentiation, following retinoic acid (RA) treatment, at the protein level. Surprisingly, heat shock treatment also triggered the down-regulation of HSP90 within 48 h at the protein level. Furthermore, the heat treatment induced cellular differentiation into neural cells. This down-regulation of HSP90 by heat treatment was shifted to an up-regulation attern after cellular differentiation in response to RA treatment. In order to clarify the functions of HSP90 in cellular differentiation, we conducted various experiments, including overexpression of HSP90 via gene transfer. We showed that the RA-induced differentiation of EC cells into a neural cell lineage was inhibited by overexpression of the HSP90α or-β isoform via the gene transfer method. On the other hand, the overexpression of HSP90β alone impaired cellular differentiation into trophoectoderm. These results show that down-regulation of HSP90 is a physiological critical event in the differentiation of human EC cells and that specific HSP90 isoforms may be involved in differentiation into specific cell lineages.

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Authors and Affiliations

  1. Department of Pathology, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Taketo Yamada, Akinori Hashiguchi, Sachiko Fukushima, Yutaka Kakita, Akihiro Umezawa, Tatsuya Maruyama & Jun-Ichi Hata

  2. Department of Internal Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Tatsuya Maruyama

  3. Department of Medical Microbiology, Lund University, University Hospital, S-205 02, Malmo, Sweden

    Sachiko Fukushima

  4. Department of Pediatric Surgery, Juntendou University School of Medicine, 2-1 Hongo Bunkyo-ku, 113, Tokyo, Japan

    Yutaka Kakita

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  1. Taketo Yamada
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  2. Akinori Hashiguchi
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  7. Jun-Ichi Hata
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Yamada, T., Hashiguchi, A., Fukushima, S. et al. Function of 90-kDa heat shock protein in cellular differentiation of human embryonal carcinoma cells. In Vitro Cell.Dev.Biol.-Animal 36, 139–146 (2000). https://doi.org/10.1290/1071-2690(2000)036<0139:FOKHSP>2.0.CO;2

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  • DOI: https://doi.org/10.1290/1071-2690(2000)036<0139:FOKHSP>2.0.CO;2

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