Akt interaction with PLC(gamma) regulates the G(2)/M transition triggered by FGF receptors from MDA-MB-231 breast cancer cells.
OBJECTIVE
Estrogen-independent breast cancer cell growth is under the control of fibroblast growth factors receptors (FGFRs), but the role of phospholipase C gamma (PLC(gamma)) and Akt, the downstream effectors activated by FGFRs, in cell proliferation is still unresolved.


METHODS
FGFRs from highly invasive MDA-MB-231 cells were expressed in Xenopus oocyte, a powerful model system to assess the G(2)/M checkpoint regulation. Under FGF1 stimulation, an analysis of the progression in the M-phase of the cell cycle and of the Akt signaling cascades were performed using the phosphatidylinositol-3-kinase inhibitor, LY294002, and a mimetic peptide of the SH3 domain of PLC(gamma).


RESULTS
Activated Akt binds and phosphorylates PLC(gamma) before Akt targets the tumor suppressor Chfr. Disruption of the Akt-PLC(gamma) interaction directs Akt binding to Chfr and accelerates the alleviation of the G(2)/M checkpoint.


CONCLUSIONS
The PLC(gamma)-Akt interaction, triggered by FGF receptors from estrogen-independent breast cancer cells MDA-MB-231, regulates progression in the M-phase of the cell cycle.
Browaeys-Poly
Edith
E
Laboratoire de Régulation des Signaux de Division, Université Lille 1 Sciences et Technologies, 59655 Villeneuve d'Ascq, France.
Perdereau
Dominique
D
Lescuyer
Arlette
A
Burnol
Anne-Françoise
AF
Cailliau
Katia
K
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008845:Microinjections; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D051966:Phospholipase C gamma / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D014982:Xenopus laevis
D017468:Receptors, Fibroblast Growth Factor; D016220:Fibroblast Growth Factor 1; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma