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 language | English |
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Pages (from-to) | 4997-5001 |
Number of pages | 5 |
Journal | Oncogene |
Volume | 21 |
Issue number | 32 |
DOIs | |
State | Published - 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.
Funders | Funder number |
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Association for Cure of Cancer | |
Melul Foundation | |
Israel Cancer Association |
Keywords
- Colon carcinoma
- Fer
- Gamma interferon
- Stat3