Syk: a new player in the field of breast cancer

Syk is ubiquitously expressed in hematopoietic cells and has been extensively studied as an effector of B cell receptor (BCR) signaling [3]. BCR engagement induces signaling cascades mediated by three families of nonreceptor tyrosine kinases [3]: the ZAP-70 family (ZAP-70, Syk), the Src family (Lyn, Fyn, Blk), and the Tec family (Btk, Itk, Etk). After BCR activation, Syk-dependent signaling pathways regulate the clonal expansion, differentiation, or apoptosis of B cells. Phospholipase C (PLC)-γ2 and phosphatidylinositol 3-kinase (PI3-K) are key targets of Syk tyrosine phosphorylation after BCR cross-linking [3]. In B cells, Syk phosphorylation of PLC-γ2 results in downstream activation of the ERK and JNK kinases [4], whereas PI3-K phosphorylation by Syk mediates Akt activity [5]. Syk also preferentially phosphorylates the α-tubulin subunits of microtubules, which has been proposed to regulate the ability of the microtubule cytoskeleton to function as a scaffold for the assembly of signaling complexes [6].In addition to breast epithelial cells, Syk expression has also been observed in other nonhematopoietic cells. For example, Syk is expressed in human hepatocytes, and use of the Syk-selective inhibitor, piceatannol, indicated that Syk is necessary for mitogen-activated protein kinase activation by G-protein coupled receptors in this cell type [7]. In human colon carcinoma cells, Syk gene expression is repressed in a p53-dependent manner, suggesting that loss of p53 function during tumorigenesis can lead to deregulated Syk activity [8].Characterization of murine Syk revealed that Syk is expressed at high levels in normal mammary glands [9]. In agreement with this latter study, recent findings of Coopman et al [2] showed that Syk is a potent modulator of breast epithelial cell growth. Coopman et al initially examined Syk mRNA and protein expression in a panel of well-characterized breast cancer cell lines, normal mammary gland tissue, and a normal breast epithelial ce