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Tumor necrosis factor α stimulates Her-2 cleavage by activated caspase-8

Xiaojun Li1, Yang Zhao, Yunfeng Zhang

  • 1Department of Oncosurgery, First Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, PR China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|August 28, 2012
PubMed
Abstract

Insights

Nuclear factor kappa B (NFĸB) counteracts tumor necrosis factor alpha (TNF-α)-induced Her-2 cleavage in breast cancer cells. This suggests NFĸB acts as an antiapoptotic factor by inhibiting Her-2 degradation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Her-2 over-expression is linked to poor prognosis in breast cancer.
  • Investigating the role of TNF-α and NFĸB in Her-2 expression is crucial.

Purpose of the Study:

  • To explore the effects of TNF-α and NFĸB on Her-2 expression in MCF-7 breast adenocarcinoma cells.
  • To elucidate the mechanism of Her-2 regulation in breast cancer.

Main Methods:

  • Utilized stably transfected MCF-7 cell lines.
  • Assessed protein and mRNA expression via Western blot and Real-time PCR.
  • Evaluated caspase-8 activity using a spectrofluorometer.

Main Results:

  • Identified Her-2 as a novel substrate for caspase-8.
  • Demonstrated TNF-α stimulation causes caspase-8-dependent Her-2 cleavage in NFĸB-deficient cells.
  • Showed NFĸB counteracts Her-2 cleavage by inducing the caspase-8 inhibitor, c-FLIP.

Conclusions:

  • Proposed a novel mechanism where NFĸB acts as an antiapoptotic factor.
  • NFĸB counteracts TNF-α-triggered Her-2 cleavage.
  • This finding offers new insights into breast cancer progression and potential therapeutic targets.

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