Proteomic analysis reveals that 14-3-3sigma is down-regulated in human breast cancer cells.
The class of molecular chaperones known as 14-3-3 is involved in the control of cellular growth by virtue of its apparent regulation of various signaling pathways, including the Raf/mitogen-activated protein kinase pathway. In breast cancer cells, the sigma form of 14-3-3 has been shown to interact with cyclin-dependent kinases and to control the rate of entry into mitosis. To test for a direct role for 14-3-3 in breast epithelial cell neoplasia, we have quantitated 14-3-3 protein levels using a proteomic approach based on two-dimensional electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF). We show here that 14-3-3sigma protein is strongly down-regulated in the prototypic breast cancer cell lines MCF-7 and MDA-MB-231 and in primary breast carcinomas as compared with normal breast epithelial cells. In contrast, levels of the alpha, beta, delta, or zeta isoforms of 14-3-3 were the same in both normal and transformed cells. The data support the idea that 14-3-3sigma is involved in the neoplastic transition of breast epithelial cells by virtue of its role as a tumor suppressor; as such, it may constitute a robust marker with clinical efficacy for this pathology.
Vercoutter-Edouart
A S
AS
Equipe Facteurs de Croissance, Laboratoire de Biologie du Développement, UPRES-EA 1033, Villeneuve d'Ascq, France.
Lemoine
J
J
Le Bourhis
X
X
Louis
H
H
Boilly
B
B
Nurcombe
V
V
Révillion
F
F
Peyrat
J P
JP
Hondermarck
H
H
D048948:14-3-3 Proteins; D001345:Autoradiography; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000378:metabolism; D005092:Exonucleases; D005095:Exoribonucleases; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011506:Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human