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

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

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


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 showed 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 pattern 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 physiologically critical event in the differentiation of human EC cells and that specific HSP90 isoforms may be involved in differentiation into specific cell lineages.

Original languageEnglish
Pages (from-to)139-146
Number of pages8
JournalIn Vitro Cellular and Developmental Biology - Animal
Issue number2
Publication statusPublished - 2000 Feb


  • 90-kDa heat shock protein
  • Differentiation
  • Human embryonal carcinoma cell
  • Retinoic acid

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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