Proteomic analysis reveals that 14-3-3 sigma is down-regulated in human breast cancer cells

The class of molecular chaperones known as 14-3-3 is involved in the contro l of cellular growth by virtue of its apparent regulation of various signal ing pathways, including the Raf/mitogen-activated protein kinase pathway. I n 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, me have quantitated 14-3-3 protein levels using a proteomic approach based on two-dimensional electrophoresis and matrix-assisted laser desorption/io nization mass spectrometry (MALDI-TOF). We show here that 14-3-3 sigma prot ein is strongly down-regulated in the prototypic breast cancer cell lines M CF-7 and MDA-MB-231 and in primary breast carcinomas as compared with norma l breast epithelial cells. In contrast, levels of the alpha, beta, delta, o r zeta isoforms of 14-3-3 mere the same in both normal and transformed cell s. The data support the idea that 14-3-3 sigma is involved in the neoplasti c transition of breast epithelial cells by virtue of its role as a tumor su ppressor; as such, it may constitute a robust marker with clinical efficacy for this pathology.