Gamma interferon down-regulates Fer and induces its association with inactive Stat3 in colon carcinoma cells

Kira Orlovsky, Livia Theodor, Hana Malovani, Yehuda Chowers, Uri Nir

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Gamma interferon (IFN-γ) is a regulator of cell growth, which suppresses the proliferation of HT-29 colon carcinoma cells. Here we show that in HT-29 cells IFN-γ transiently increased the cellular level of the tyrosine kinase Fer, whose functioning was found to be essential for the proliferation of malignant cell-lines. The transient elevation in the level of Fer, was followed by its down-regulation, an effect which was most prominent after 6-8 h of IFN-γ treatment. Up- and down-regulation of Per was paralleled by the activation and subsequent deactivation of Stat3, which is a potent oncogene and a putative substrate of the tyrosine kinase Fer. Moreover, IFN-γ induced the association of Fer and Stat3 and the newly formed complex was most stable at the down-regulated states of the two proteins. Formation of the Fer/Stat3 complex was accompanied by an attenuation in cell-cycle progression and accumulation of cells in the G1 phase. Thus, Fer and Stat3 are two proliferation-promoting factors whose down-regulation could contribute to the cytostatic activity of IFN-γ in colon carcinoma cells.

Original languageEnglish
Pages (from-to)4997-5001
Number of pages5
JournalOncogene
Volume21
Issue number32
DOIs
StatePublished - 25 Jul 2002

Bibliographical note

Funding Information:
We thank U Caro for help with the flow-cytometry analysis. This work was supported by grants from the Association for Cure of Cancer of the Prostate (CaPCURE) and from the Melul Foundation; the Israel Cancer Association in memory of the late Prof N Trainin.

Funding

We thank U Caro for help with the flow-cytometry analysis. This work was supported by grants from the Association for Cure of Cancer of the Prostate (CaPCURE) and from the Melul Foundation; the Israel Cancer Association in memory of the late Prof N Trainin.

FundersFunder number
Association for Cure of Cancer
Melul Foundation
Israel Cancer Association

    Keywords

    • Colon carcinoma
    • Fer
    • Gamma interferon
    • Stat3

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