Akt interaction with PLC(gamma) regulates the G(2)/M transition triggered by FGF receptors from MDA-MB-231 breast cancer cells.

Abstract

BACKGROUND/AIM:

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.

MATERIALS AND 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.

CONCLUSION:

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.

• Authors: Edith Browaeys-Poly, Dominique Perdereau, Arlette Lescuyer, Anne-Françoise Burnol, Katia Cailliau
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 12 Pg. 4965-9 (Dec 2009) ISSN: 1791-7530 [Electronic] Greece
• PMID: 20044603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Fibroblast Growth Factor
• Fibroblast Growth Factor 1
• Proto-Oncogene Proteins c-akt
• Phospholipase C gamma

Topics

• Animals
• Blotting, Western
• Breast Neoplasms (metabolism)
• Cell Division (physiology)
• Electrophysiology
• Female
• Fibroblast Growth Factor 1 (metabolism)
• G2 Phase (physiology)
• Humans
• Immunoprecipitation
• Microinjections
• Oocytes (cytology, physiology)
• Phospholipase C gamma (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptors, Fibroblast Growth Factor (metabolism)
• Signal Transduction
• Xenopus laevis