IFNγ sensitization to TRAIL-induced apoptosis in human thyroid carcinoma cells by upregulating Bak expression

Su He Wang, Emese Mezosi, Julie M. Wolf, Zhengyi Cao, Saho Utsugi, Paul G. Gauger, Gerard M. Doherty, James R. Baker

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

TRAIL preferentially induces apoptosis in tumor cells and virus-infected cells. Unlike other tumor necrosis factor family members, TRAIL does not kill cells from most normal tissues and has thus been proposed as a promising new cancer treatment. Our study demonstrated that IFNγ combined with TRAIL can trigger apoptosis in vitro in several resistant thyroid tumor cell lines, such as thyroid anaplastic carcinoma cells (ARO cells), while either agent alone exerts only a minimal effect. We further tested this effect on a mouse thyroid tumor model, when in vivo tumor growth was also significantly inhibited by this combination. The mechanism of how IFNγ sensitized thyroid carcinoma cells to TRAIL-induced apoptosis was investigated by screening global gene alterations in ARO cells treated with IFNγ. Microarray data revealed that a proapoptotic gene, Bak, is markedly upregulated by IFNγ, and this was confirmed by RNase protection assay. Western blot analysis also showed a significant increase in Bak at the protein level. Upregulation of Bak and sensitization for apoptosis by IFNγ was blocked by overexpression of antisense Bak in ARO cells. Furthermore, overexpression of Bak sensitized ARO cell to TRAIL-induced apoptosis without the need for IFNγ pretreatment. This suggests that Bak is a regulatory molecule involved in IFNγ- facilitated TRAIL-mediated apoptosis in thyroid cancer cells.

Original languageEnglish
Pages (from-to)928-935
Number of pages8
JournalOncogene
Volume23
Issue number4
DOIs
Publication statusPublished - Jan 29 2004

Fingerprint

Thyroid Neoplasms
Apoptosis
Carcinoma
Thyroid Gland
bcl-2 Homologous Antagonist-Killer Protein
Neoplasms
Oncogenic Viruses
Ribonucleases
Tumor Cell Line
Genes
Up-Regulation
Tumor Necrosis Factor-alpha
Western Blotting
Growth

Keywords

  • Apoptosis
  • Bak
  • IFNγ
  • Thyroid cancer
  • TRAIL

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

IFNγ sensitization to TRAIL-induced apoptosis in human thyroid carcinoma cells by upregulating Bak expression. / Wang, Su He; Mezosi, Emese; Wolf, Julie M.; Cao, Zhengyi; Utsugi, Saho; Gauger, Paul G.; Doherty, Gerard M.; Baker, James R.

In: Oncogene, Vol. 23, No. 4, 29.01.2004, p. 928-935.

Research output: Contribution to journalArticle

Wang, SH, Mezosi, E, Wolf, JM, Cao, Z, Utsugi, S, Gauger, PG, Doherty, GM & Baker, JR 2004, 'IFNγ sensitization to TRAIL-induced apoptosis in human thyroid carcinoma cells by upregulating Bak expression', Oncogene, vol. 23, no. 4, pp. 928-935. https://doi.org/10.1038/sj.onc.1207213
Wang, Su He ; Mezosi, Emese ; Wolf, Julie M. ; Cao, Zhengyi ; Utsugi, Saho ; Gauger, Paul G. ; Doherty, Gerard M. ; Baker, James R. / IFNγ sensitization to TRAIL-induced apoptosis in human thyroid carcinoma cells by upregulating Bak expression. In: Oncogene. 2004 ; Vol. 23, No. 4. pp. 928-935.
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