In addition to MAPK pathway, the PI3K/Akt pathway is another critical pathway involved in cell survival and has been shown to be constitutivelsy active in ovarian cancer cell lines [27, 28]. However, little is known about the relation of Lewis y and the PI3K/Akt pathway in the development and management of ovarian cancer. In an effort to understand the mechanism of action VS-4718 of Lewis y, we focused on investigating its effect on the PI3K/Akt pathway. In this study, we found the PI3K/Akt pathway was aberrantly activited by Lewis y antigen and PI3K/Akt pathway

is necessary for Lewis y enhancing growth of RMG-I cells. It was verified by (1) increased tyrosine phosphorylation of Akt in α1,2-FT transfected cells. (2) blockage of

GDC-0994 cell surface Lewis y by anti-Lewis y antibody resulted in significant attenuation of the phosphorylation of Akt, as well as the difference in phosphorylation intensity among two cell lines. (3) in the presence of PI3K inhibitor LY294002, Lewis y no longer conferred a growth advantage in RMG-I-H cell. One of the crucial downstream targets of PI3K is the serine/threonine kinase Akt. Active Akt causes a variety of biological effects, including suppression of apoptosis by phosphorylation and inactivation of several targets along pro-apoptotic pathways. In particular, activated Akt is able to phosphorylate a variety of downstream substrates, e.g., Raf and I-K (a kinase that regulates the NF-κB transcription factor) [29]. A number of studies have demonstrated that the patients with increased p-Akt had a significant survival 17-DMAG (Alvespimycin) HCl disadvantage compared to patients with lower Akt phosphorylation, and the patients with ovarian cancer suggested p-Akt overexpression as an independent prognostic indicator [30–32]. To our knowledge, this is the first report showing that overexpression of Lewis y antigen could significantly enhance proliferation of ovarian cancer cells through upregulating PI3K/Akt pathway. Lewis y is mainly distributed at the plasma

membrane of cancer cells [33], and carried by different Dinaciclib cost glycolipids [34] and glycoproteins, such as CD44v6 [35], Muc6 [36] and epidermal growth factor receptor (EGFR) [37], which are related to carcinogenesis. Studies showed that changes in glycosyltransferase expression might affect structure of carbohydrate chains on cell surface receptors and therefore impacted the expression and function of those glycoprotein receptors [38, 39]. It has been reported that transfection of the sense cDNA of N -acetylglucosaminyltransferase(GnT)-V, an enzyme associated with cancer progression and metastasis, into human H7721 hepatocarcinoma cells resulted in an increase in the level of GlcNAcβ1,6 Manα1,6-branch (GnT-V product) on the N-glycans of EGFR, this promoted the tyrosine autophosphorylation of EGFR [40].