Overexpression of metastasis-associated protein 2 is associated with hepatocellular carcinoma size and differentiation.
OBJECTIVE
Metastasis is a multistep event in which neoplastic cells detach from the tumor, migrate, disseminate, extravasate, and eventually proliferate at the secondary distant sites. Hepatocellular carcinoma (HCC) is characterized by hypervascularity and frequent metastasis. Recently, metastasis-associated proteins were identified and named metastatic tumor antigens (MTA) 1, 2, and 3. They have been found to be contained in the nucleosome remodeling and histone deacetylase complex. MTA2 has been reported to interact with p53 and inhibit p53-mediated cell growth arrest and apoptosis by deacetylation. Although it has been reported that the expression of MTA1 is related to tumor progression and metastasis, it is still unclear how MTA2 is involved in HCC. In this study, we found that the overexpression of MTA2 is associated with HCC size and differentiation after hepatectomy.


METHODS
The expression of MTA2 was examined in 506 human HCC samples that underwent hepatic resection using tissue microarray. The expression of MTA2 was classified into 0, 1, 2, and 3, based on immunoreactivity.


RESULTS
The expression of MTA2 was predominantly localized to the nucleus. MTA2 was detected in 487 (96.2%) of the 506 human HCC samples. Notably, the MTA2 expression level strongly increased depending on the size and differentiation of HCC.


CONCLUSIONS
These findings indicate a tight correlation between the MTA2 expression level and HCC size and differentiation. Therefore, MTA2 might be a predictor of aggressive phenotypes and a possible target molecule for anticancer drug design in human HCC.
Lee
Hyunseung
H
NeuroVascular Coordination Research Center, College of Pharmacy, Seoul National University, Seoul, Korea.
Ryu
Soo Hyung
SH
Hong
Soon Sun
SS
Seo
Dong Dae
DD
Min
Hyun Joo
HJ
Jang
Myoung Kuk
MK
Kwon
Ho Jeong
HJ
Yu
Ensil
E
Chung
Young-Hwa
YH
Kim
Kyu-Won
KW
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000737:chemistry; D049109:Cell Proliferation; D005260:Female; D006498:Hepatectomy; D006655:Histone Deacetylases / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012097:Repressor Proteins / Q000032:analysis*; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D012097:Repressor Proteins; C120917:MTA2 protein, human; D006655:Histone Deacetylases