Interferon-resistant Daudi cell line with a stat2 defect is resistant to apoptosis induced by chemotherapeutic agents

Ziyun Du, Meiyun Fan, Jong Gwan Kim, Dara Eckerle, Leonard Lothstein, Lai Wei, Lawrence Pfeffer

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Interferon-α (IFNα) has shown promise in the treatment of various cancers. However, the development of IFN resistance is a significant drawback. Using conditions that mimic in vivo selection of IFN-resistant cells, the RST2 IFN-resistant cell line was isolated from the highly IFN-sensitive Daudi human Burkitt lymphoma cell line. The RST2 cell line was resistant to the antiviral, antiproliferative, and gene-induction actions of IFNα. Although STAT2 mRNA was present, STAT2 protein expression was deficient in RST2 cells. Avariant STAT2 mRNA, which resulted from alternative splicing within the intron between exon 19 and 20, was expressed in several human cell lines but at relatively high levels in RST2 cells. Most importantly, the RST2 line showed an intrinsic resistance to apoptosis induced by a number of chemotherapeutic agents (camptothecin, staurosporine, and doxorubicin). Expression of STAT2 in RST2 cells not only rescued their sensitivity to the biological activities of IFNs but also restored sensitivity to apoptosis induced by these chemotherapeutic agents. The intrinsic resistance of the RST2 cells to IFN as well as chemotherapeutic agents adds a new dimension to our knowledge of the role of STAT2 as it relates to not only biological actions of IFN but also resistance to chemotherapy-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)27808-27815
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number41
DOIs
StatePublished - Oct 9 2009

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Interferons
Cells
Apoptosis
Cell Line
Defects
STAT2 Transcription Factor
Camptothecin
Messenger RNA
Chemotherapy
Staurosporine
Burkitt Lymphoma
Alternative Splicing
Bioactivity
Doxorubicin
Introns
Antiviral Agents
Exons
Genes
Drug Therapy
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Interferon-resistant Daudi cell line with a stat2 defect is resistant to apoptosis induced by chemotherapeutic agents. / Du, Ziyun; Fan, Meiyun; Kim, Jong Gwan; Eckerle, Dara; Lothstein, Leonard; Wei, Lai; Pfeffer, Lawrence.

In: Journal of Biological Chemistry, Vol. 284, No. 41, 09.10.2009, p. 27808-27815.

Research output: Contribution to journalArticle

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