The antiapoptotic effect of fibroblast growth factor-2 is mediated through nuclear factor-κB activation induced via interaction between Akt and IκB kinase-β in breast cancer cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2005

The antiapoptotic effect of fibroblast growth factor-2 is mediated through nuclear factor-κB activation induced via interaction between Akt and IκB kinase-β in breast cancer cells

Résumé

Fibroblast growth factor-2 (FGF-2) is known for its mitogenic and motogenic effects on breast cancer cells. Here, we demonstrate that FGF-2 is also a potent stimulator of breast cancer cell survival, as it counteracts the apoptotic activity of the C2 ceramide analogue and various chemotherapeutic agents (5-fluorouracil, camptothecin, etoposide) in MCF-7, T47-D and BT-20 cells. The use of pharmacological inhibitors (PD98059, wortmannin, LY294002, SN50) and transfection with negative dominants (IkappaBm, p110(PI3K (phosphoinositide 3-kinase))*DeltaK, AktND) or small interfering RNA targeted against Akt indicated that PI3K/Akt and nuclear factor-kappaB (NF-kappaB), but not p42/p44 MAP-kinases, were required to stimulate FGF-2 antiapoptotic activity. The activation of NF-kappaB was dependent on PI3K/Akt, and using a combination of approaches based on immunoprecipitation, Western blotting and proteomics (two-dimensional electrophoresis and mass spectrometry), we identified the beta form of IkappaB kinase (IKKbeta) as a target of Akt signaling. The selective disruption of IKKbeta using small interfering RNA induced a potent inhibition of Akt-mediated activation of NF-kappaB and cell survival, indicating the functional involvement of IKKbeta in FGF-2 antiapoptotic signaling. Together, these results demonstrate Akt/IKKbeta interaction in NF-kappaB pathways, thereby emphasizing the potential of these proteins as therapeutic targets in breast cancer.

Dates et versions

hal-02477627 , version 1 (13-02-2020)

Identifiants

Citer

Franck Vandermoere, Ikram El Yazidi-Belkoura, Eric Adriaenssens, Jérôme Lemoine, Hubert Hondermarck. The antiapoptotic effect of fibroblast growth factor-2 is mediated through nuclear factor-κB activation induced via interaction between Akt and IκB kinase-β in breast cancer cells. Oncogene, 2005, 24 (35), pp.5482-5491. ⟨10.1038/sj.onc.1208713⟩. ⟨hal-02477627⟩

Collections

CNRS UNIV-LILLE
19 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More