Deregulated expression of Notch receptors in human hepatocellular carcinoma.
OBJECTIVE
Notch signaling controls cellular differentiation and proliferation. Deregulated expression of Notch receptors is observed in a growing number of malignant tumours, however, the role of Notch signaling in hepatocellular carcinoma is still unknown. To address this, the expression of Notch receptors in human hepatocellular carcinoma was examined in both protein and ribonucleic acid levels.


METHODS
Fifty-three hepatocellular carcinoma tissue sections were detected by immunohistochemistry. Three paired fresh surgical hepatocellular carcinoma and adjacent nontumour liver samples were analyzed by Western blot and reverse transcriptase polymerase chain reaction. Immunohistochemistry, Western blot and reverse transcriptase polymerase chain reaction are reliable methods to examine the expression of protein and RNA.


RESULTS
All of the four Notch receptors were expressed in the neoplastic cells of hepatocellular carcinoma tissues with different intensity and extensity. Notch1 and Notch4 were expressed in both cytoplasm and nucleus, and all of the nuclear staining showed up in the cytoplasm-positive cases. Cytoplasmic and nuclear Notch1 was detected in 88.7% (47/53) and 9.4% (5/53) of hepatocellular carcinoma tissues, respectively; positive rates of Notch4 were 67.9% (36/53) in cytoplasm and 52.8% (31/53) in nucleus. Notch2 and Notch3 were only in cytoplasm, with positive rates of 26.4% (14/53) and 52.8% (28/53), respectively. Compared with adjacent nontumour liver, Notch1 (cytoplasmic) and Notch4 (nuclear) were up-regulated (P<0.05, P<0.05), Notch2 was down-regulated (P<0.05), while Notch1 (nuclear), Notch3 and Notch4 (cytoplasmic) showed no difference between hepatocellular carcinoma and adjacent nontumour liver. Western blot and reverse transcriptase polymerase chain reaction analysis showed a consistent result.


CONCLUSIONS
Our findings indicate that the expression of Notch receptors was deregulated and Notch signaling might be involved in the development of hepatocellular carcinoma.
Gao
J
J
Department of Digestive Diseases, Wuhan General Hospital, Guangzhou Command PLA, Wuhan, Hubei Province, PR China.
Song
Z
Z
Chen
Y
Y
Xia
L
L
Wang
J
J
Fan
R
R
Du
R
R
Zhang
F
F
Hong
L
L
Song
J
J
Zou
X
X
Xu
H
H
Zheng
G
G
Liu
J
J
Fan
D
D
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification; D051881:Receptor, Notch1 / Q000378:metabolism; D051883:Receptor, Notch2 / Q000378:metabolism; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C499374:NOTCH3 protein, human; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D012313:RNA