The positive reaction

located in cytosol was stained in brown. The color of the stain is positively correlated to the protein expression. The IOD of each group revealed that in the SHG44 -DDK-1 the expression of bax and caspase-3 increased, whereas JIB04 clinical trial the expression of bcl-2 decreased (Table 1). Figure 6 Bax, bcl-2 and caspase-3 protein expression inthree groups cell (×400). (A) Bax normal SHG44;(B)Bax SHG44-EV; (C)Bax SHG44-DKK-1;(D) Bcl-2 normal SHG44 (E)Bcl-2 SHG44-EV; (F)Bcl-2 SHG44-DKK-1; (G)Caspase-3 normal SHG44; (H)Caspase-3 SHG44-EV; (I)Caspase-3 SHG44-DKK-1 Table 1 Bax, bcl-2 and caspase-3 expression (in IOD) in normal SHG44, SHG44-EV and SHG44-DKK-1 cells.   Bax protein expression Bcl-2 protein express Caspase-3 protein express   n = 6 IOD n = 6 IOD

n = 6 IOD normal SHG44 2323 ± 305 5046 ± 521 1845 ± 126 SHG44-EV 2623 ± 420 6417 ± 462 1920 ± 231 SHG44-DKK-1 4567 ± 598* 2900 ± 302* 3944 ± 511* *P < 0.05 Discussion The family of DKK genes is a small, but conservative gene family, which is composed of DKK-1, DKK-2, DKK-3, DKK-4 and DKKL-1 (also called Soggy), a DKK-3 related gene. DKK proteins possess different structure and function, but many of them play important roles in various human EPZ-6438 nmr diseases [2]. DKK-1 is the most well-studied gene in the DKK gene family. It is mapped to chromosome 10q11.2 [11] and encodes a secretory glucoprotein, which contains 266 amino acids with a molecular weight of 35KD. The glucoprotein contains a N-terminal signal peptide of 31 amino acids, two conserved cysteine-rich domains and a C-terminus with glycosylation function. DKK-1 acts as a wnt antagonist by forming a complex with the transmembrane proteins

Kremen1 and 2 (Krm1/2) and low- density-lipoprotein 5/6(LRP5/6). The complex is then removed through endocytosis, resulting in the removal of LRP5/6 from the cell surface [12, 13] Recent studies revealed that DKK-1 is not only an antagonist of classic Wnt/β-cantenin signaling many pathway but also a direct regulator of transcription of its target genes [14]. The function of DKK-1 in tumor progression has been shown to be complicated and even controversial. A number of studies showed that DKK-1 induces apoptosis and inhibits tumor growth [15–17] DKK-1 expression in primary medulloblastoma cells is significantly down-regulated relative to normal cerebellum and Eltanexor transfection of a DKK-1 gene construct into D283 cell line suppresses medulloblastoma tumor growth [18]. In addition, adenoviral vector-mediated expression of DKK-1 in medulloblastoma cells significantly increases the apoptosis rate. DKK-1, however, is also reported to be overexpressed in tissues and serum of lung cancers and esophageal squamous cell carcinoma, suggesting that DKK-1 may act as pro-oncogene [19].