The inhibitory effect of p75 neurotrophin receptor on growth of human hepatocellular carcinoma cells.
p75 neurotrophin receptor (p75NTR), a member of the TNF receptor superfamily, is a focus for study at present. Up to now, its role and functions in hepatocellular carcinoma were not fully elucidated. In this study, we investigated the expression of p75NTR in hepatocellular carcinoma and the impact of its alteration on tumor growth. We found that the expression of p75NTR was decreased significantly in 158 cases of hepatocellular carcinoma tissues as compared with their adjacent noncancerous counterparts, and its expression was also significantly decreased in various human hepatocellular carcinoma cell lines. Down-regulating p75NTR by specific siRNA promoted the growth of normal liver cell lines, whereas up-regulating p75NTR inhibited the growth of hepatocellular carcinoma cell lines in vitro and caused dramatic attenuation of tumor growth in vivo by induction of cell cycle arrest. Furthermore, we found that up-regulating p75NTR could down-regulate the expression of cyclin A, cyclin D1, cyclin E, cdk2, p-Rb and PCNA, but up-regulate the expression of Rb. Conversely, the results were inverse when p75NTR was down-regulated by specific siRNA. Therefore, we provided the evidence that p75NTR was a potential tumor suppressor and might be used as a therapeutic target for hepatocellular carcinoma.
Yuanlong
He
H
State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, 17 Changle Western Road, Xi'an, Shaanxi Province 710032, PR China.
Haifeng
Jin
J
Xiaoyin
Zhang
Z
Jialin
Song
S
Jie
Liu
L
Li
Yan
Y
Huahong
Xie
X
Jiugang
Song
S
Yanglin
Pan
P
Kaichun
Wu
W
Jie
Ding
D
Daiming
Fan
F
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism / Q000502:physiology*
D034741:RNA, Small Interfering; D020800:Receptor, Nerve Growth Factor