Reduced T-cadherin expression and promoter methylation are associated with the development and progression of hepatocellular carcinoma.
Loss of T-cadherin expression has been reported in a number of human cancers. We previously reported that T-cadherin re-expression suppressed cell growth and motility in glioma. Here, we report that the T-cadherin expression was significantly decreased in human hepatocellular carcinoma (HCC) compared to adjacent normal liver. In addition, T-cadherin expression in HCC with metastasis was significantly lower than in HCC without metastasis. To determine the mechanism underlying the reduced T-cadherin expression in HCC, we examined T-cadherin promoter methylation. We found that methylation of the T-cadherin promoter was present in 40% of HCC, but absent in all adjacent liver tissues. In the HCC with T-cadherin promoter methylation, the T-cadherin expression was significantly decreased compared to HCC without methylation. To provide a functional link between T-cadherin promoter methylation and T-cadherin growth regulation, we used the HepG2 hepatoma cell line that exhibits T-cadherin promoter methylation. Treatment of HepG2 cells with the demethylating agent 5-aza-2-deoxycytidine resulted in increased T-cadherin expression and reduced cell proliferation. These results demonstrate that the T-cadherin down-regulation by promoter methylation is associated with the development and progression of HCC, and suggest that T-cadherin is an important tumor suppressor in liver cancer.
Yan
Qun
Q
Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong Universty of Science and Technology, Wuhan 430030, P.R. China.
Zhang
Zhi-Fa
ZF
Chen
Xiao-Ping
XP
Gutmann
David H
DH
Xiong
Min
M
Xiao
Zhen-Yu
ZY
Huang
Zhi-Yong
ZY
D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D018450:Disease Progression; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D004791:Enzyme Inhibitors; C099972:H-cadherin; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine