Involvement of interferon regulatory factor 1 and S100C/A11 in growth inhibition by transforming growth factor β1 in human hepatocellular carcinoma cells

Masahiro Miyazaki, Masakiyo Sakaguchi, Ichiro Akiyama, Yoshihiko Sakaguchi, Seishi Nagamori, Nam Ho Huh

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Growth inhibition by transforming growth factor (TGF)-β1 has been attributed to the induction of cyclin-dependent kinase inhibitors, among which p21/Waf1 plays a major role in many biological contexts. In the present study, two new intracellular mediators for the induction of p21/Wafl by TGF-β1 were identified in a human hepatocellular carcinoma cell line (JHH-5) expressing mutant-type p53. After addition of TGF-β1 to JHH-5 cells, a marked increase of the p21/Waf1 expression preceded the inhibition of DNA synthesis. Expression of IFN regulatory factor (IRF)-1, a known transacting factor for p21/Waf1 promoter, was elevated just before or in parallel with the increase of p21/Waf1. Transduction of antisense IRF-1 inhibited the increase in p21/Waf1 in JHH-5 cells treated with TGF-β1 and partially released the cells from the growth arrest by TGF-β1. Expression of S100C/A11, a member of the Ca 2+-binding S100 protein family, also markedly increased after addition of TGF-β1. S100C/A11 protein was translocated to and accumulated in nuclei of TGF-β1-treated JHH-5 cells, where p21/Waf1 was concomitantly accumulated. When a recombinant S100C/A11 protein was introduced into nuclei of JHH-5 cells, DNA synthesis was markedly inhibited in a dose-dependent manner in the absence of TGF-β1. Prior transfection of p21/Waf1-targeted small Interfering RNA efficiently blocked decrease of DNA synthesis in JHH-5 cells caused by TAT-S100C/A11 or TGF-β1 and markedly inhibited expression of p21/Waf1 protein in the cells. These results indicate that IRF-1 and S100C/A11 mediate growth inhibition by TGF-β1 via induction of p21/Waf1.

Original languageEnglish
Pages (from-to)4155-4161
Number of pages7
JournalCancer Research
Volume64
Issue number12
DOIs
Publication statusPublished - Jun 15 2004

Fingerprint

Interferon Regulatory Factor-1
Transforming Growth Factors
Hepatocellular Carcinoma
Growth
DNA
Proteins
Cyclin-Dependent Kinases
S100 Proteins
Small Interfering RNA
Transfection
Carrier Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Involvement of interferon regulatory factor 1 and S100C/A11 in growth inhibition by transforming growth factor β1 in human hepatocellular carcinoma cells. / Miyazaki, Masahiro; Sakaguchi, Masakiyo; Akiyama, Ichiro; Sakaguchi, Yoshihiko; Nagamori, Seishi; Huh, Nam Ho.

In: Cancer Research, Vol. 64, No. 12, 15.06.2004, p. 4155-4161.

Research output: Contribution to journalArticle

Miyazaki, Masahiro ; Sakaguchi, Masakiyo ; Akiyama, Ichiro ; Sakaguchi, Yoshihiko ; Nagamori, Seishi ; Huh, Nam Ho. / Involvement of interferon regulatory factor 1 and S100C/A11 in growth inhibition by transforming growth factor β1 in human hepatocellular carcinoma cells. In: Cancer Research. 2004 ; Vol. 64, No. 12. pp. 4155-4161.
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AU - Nagamori, Seishi

AU - Huh, Nam Ho

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