Expression of epithelial cell adhesion molecule and proliferating cell nuclear antigen in diethylnitrosamine-induced hepatocarcinogenesis in mice.
Expression of epithelial cell adhesion molecule and proliferating cell nuclear antigen in diethylnitrosamine-induced hepatocarcinogenesis in mice.
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DOI：
10.3892/etm.2012.751
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发表时间：
2013-01
影响因子：
2.7
通讯作者：
Ryu DY
中科院分区：
文献类型：
--
作者：
Kang JS;Kang HG;Park YI;Lee H;Park K;Lee YS;Kim S;Ryu DY
为了阐明干细胞在肝癌发生中的作用，研究了上皮细胞粘附分子（EpCAM）和增殖细胞核抗原（PCNA）在小鼠肝癌和胚胎细胞系中的表达。10只ICR小鼠在14日龄时用二乙基亚硝胺（DEN）治疗，并在DEN治疗后36周处死以获得肝肿瘤。小鼠胚胎干细胞，肝祖细胞和肝细胞样细胞，分别代表0，22和40天的分化，在体外处理DEN在四个剂量（0，1，5和15 mM; G1，G2，G3和G4，分别）为24小时和RNA分离。从DEN处理的小鼠中获得总共71个肝肿瘤。EpCAM的表达主要在肝肿瘤细胞中增加，尽管在周围视觉正常的细胞中也检测到。双重染色显示EpCAM和PCNA在许多肿瘤细胞中共表达。体外实验中，与对照组（G1）相比，G4组第0天EpCAM表达量显著增加（P<0.01），G2、G3和G4组第40天EpCAM表达量显著增加（P<0.01）。G3、G4在第0天、G2、G3、G4在第22天、G2在第40天与相应时间点的G1比较，PCNA表达差异有显著性（P <0.01）。总之，在DEN诱导的肿瘤中EpCAM和PCNA的表达增加，并且在培养的细胞中DEN处理改变了EpCAM和PCNA的表达。这表明EpCAM表达可能在成体肝干细胞向肝细胞分化的后代中受到调节，并且可能在DEN诱导的肝癌发生过程中增加。
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.
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影响因子：
13.5
作者：
Turner, Rachael;Lozoya, Oswaldo;Wang, Yunfang;Cardinale, Vincenzo;Gaudio, Eugenio;Alpini, Gianfranco;Mendel, Gemma;Wauthier, Eliane;Barbier, Claire;Alvaro, Domenico;Reid, Lola M.
通讯作者：
Reid, Lola M.
影响因子：
9.7
作者：
DIWAN, BA;RICE, JM;LYNCH, PH
通讯作者：
LYNCH, PH
影响因子：
1.5
作者：
Pitot, HC;Dragan, YP;Campbell, H
通讯作者：
Campbell, H
影响因子：
4.7
作者：
TAMANO, S;MERLINO, GT;WARD, JM
通讯作者：
WARD, JM
影响因子：
3.6
作者：
VESSELINOVITCH, SD;KOKA, M;RAO, KVN
通讯作者：
RAO, KVN