Expression of epithelial cell adhesion molecule and proliferating cell nuclear antigen in diethylnitrosamine-induced hepatocarcinogenesis in mice

Abstract

To clarify the role of stem cells in hepatocarcinogenesis, the expression of epithelial cell adhesion molecule (EpCAM) and proliferating cell nuclear antigen (PCNA) was investigated in mouse hepatic tumors and embryonic cell lineages. Ten ICR mice were treated with diethylnitrosamine (DEN) at 14 days of age and sacrificed at 36 weeks subsequent to DEN treatment to obtain the hepatic tumors. Mouse embryonic stem cells, hepatic progenitor cells and hepatocyte-like cells, representing 0, 22 and 40 days of differentiation, respectively, were treated in vitro with DEN at four doses (0, 1, 5 and 15 mM; G1, G2, G3 and G4, respectively) for 24 h and RNA was isolated. A total of 71 hepatic tumors were obtained from the DEN-treated mice. EpCAM expression was increased mainly in hepatic tumor cells, although it was also detected in the surrounding visually normal cells. Double staining showed that EpCAM and PCNA were co-expressed in numerous tumor cells. In vitro, EpCAM expression was significantly different for G4 at day 0 (P<0.01) and for G2, G3 and G4 at day 40 (P<0.01) compared with the control (G1) at the corresponding time-point. PCNA expression was significantly different for G3 and G4 at day 0 (P<0.01), for G2, G3 and G4 at day 22 (P<0.01) and for G2 at day 40 (P<0.01) compared with G1 at the corresponding time-point. In summary, the expression of EpCAM and PCNA was increased in DEN-induced tumors and the expression of EpCAM and PCNA was altered by DEN treatment in cultured cells. This suggests that EpCAM expression may be modulated in the progeny of adult liver stem cells during their differentiation toward hepatocytes and may be increased during DEN-induced hepatocarcinogenesis.

Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8+T Lymphocytes

“…Here we detected the levels of several markers for tumor growth and apoptosis. Proliferating cell nuclear antigen (PCNA) and phosphorylation of protein kinase B (Akt) are markers for tumor growth [32, 33]. DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a key marker for tumor apoptosis [34, 35].…”

The effect of capsaicin and diethylnitrosamine on mouse nephrotoxicity, hepatotoxicity and hepatocarcinogenesis

“…Normal liver tissue showed in few cases only weak PCNA immunoreactivity whereas the number and intensity was increasing in cirrhotic liver and mostly in HCC (Ojanguren et al 1993;Mun et al 2006). When PCNA expression was investigated in the liver of DEN-treated mice, it tended to increase, pointing to enhanced proliferation of hepatocytes (Chuang et al 2000;Sun et al 2012;Kang et al 2013). On the contrary, in our study the proliferation rate was decreased in DEN-treated animals compared to the control group.…”

Expression of neighbor of Punc E11 in hepatocarcinogenesis induced by diethylnitrosamine

“…In the present study, we detected high expression levels of Nope in DEN-treated hepatic lineage cells. DEN, a wellknown hepatocarcinogen, is widely used in mouse liver cancer models (27)(28)(29)(30)(31)(32). Expression of E-cadherin and AFP was also highly elevated in DEN-treated cells as compared to untreated cells.…”