Inactivation of heat shock factor Hsf4 induces cellular senescence and suppresses tumorigenesis In Vivo

Xiongjie Jin, Binnur Eroglu, Wonkyoung Cho, Yukihiro Yamaguchi, Dimitrios Moskofidis, Nahid F Mivechi

Research output: Contribution to journalArticle

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Abstract

Studies suggest that Hsf4 expression correlates with its role in cell growth and differentiation. However, the role of Hsf4 in tumorigenesis in vivo remains unexplored. In this article, we provide evidence that absence of the Hsf4 gene suppresses evolution of spontaneous tumors arising in p53- or Arf-deficient mice. Furthermore, deletion of hsf4 alters the tumor spectrum by significantly inhibiting development of lymphomas that are normally observed in the majority of mice lacking p53 or Arf tumor suppressor genes. Using mouse embryo fibroblasts deficient in the hsf4 gene, we have found that these cells exhibit reduced proliferation that is associated with induction of senescence and senescence-associated β-galactosidase (SA-β-gal). Cellular senescence in hsf4-deficient cells is associated with the increased expression of the cyclin-dependent kinase inhibitors, p21 and p27 proteins. Consistent with the cellular senescence observed in vitro, specific normal tissues of hsf4 -/- mice and tumors that arose in mice deficient in both hsf4 and p53 genes exhibit increased SA-β-gal activity and elevated levels of p27 compared with wild-type mice. These results suggest that hsf4 deletion-induced senescence is also present in vivo. Our results therefore indicate that Hsf4 is involved in modulation of cellular senescence, which can be exploited during cancer therapy.

Original languageEnglish (US)
Pages (from-to)523-534
Number of pages12
JournalMolecular Cancer Research
Volume10
Issue number4
DOIs
StatePublished - Apr 1 2012

Fingerprint

Cell Aging
Shock
Carcinogenesis
Hot Temperature
Galactosidases
Neoplasms
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
p53 Genes
Tumor Suppressor Genes
Genes
Cell Differentiation
Lymphoma
Embryonic Structures
Fibroblasts
Growth
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Inactivation of heat shock factor Hsf4 induces cellular senescence and suppresses tumorigenesis In Vivo. / Jin, Xiongjie; Eroglu, Binnur; Cho, Wonkyoung; Yamaguchi, Yukihiro; Moskofidis, Dimitrios; Mivechi, Nahid F.

In: Molecular Cancer Research, Vol. 10, No. 4, 01.04.2012, p. 523-534.

Research output: Contribution to journalArticle

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