Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: Relationship to vascular invasion and estrogen receptor-alpha.
The morbidity and mortality experienced by cancer patients is mainly due to the invasion and metastasis of the primary tumor. Recently, a potential metastasis-associated gene and its product, the metastatic tumor antigen 1 (MTA1), were identified; this gene has been found to be overexpressed in a variety of cancers. MTA1 is also known as a potent co-repressor of estrogen receptor element transcription in breast cancer cells. The expression of MTA1 in hepatocellular carcinoma (HCC) and its potential relationship to metastasis and to estrogen receptor alpha (ER-alpha) expression has not been examined, forming the basis for this study. Paraffin sections of 45 HCC specimens, 4 different HCC cell lines, and normal hepatocyte cell line (h NHeps) were immunostained with MTA1 and ER-alpha antibodies. In addition, we examined, by Western blotting, the MTA1 and ER-alpha expression levels in 4 human HCC lines (HepG2 [wild p53], HLE, HLF, and HuH-7 [mutant p53]). MTA1 was overexpressed in HCC cells versus nonmalignant hepatocytes in 31 of 45 HCC specimens (69%). Its expression was predominantly localized to the nucleus or cytoplasm of HCC cells. Nineteen of 20 HCC (95%) specimens with vascular invasion displayed strong MTA1 expression. Overexpression of MTA1 also significantly correlated with large tumor size. The cytoplasmic and nuclear immunoreactivity for ER-alpha was present in HCC specimens in 46% and 12%, respectively. Expression of MTA1 inversely correlated with the nuclear localization of ER-alpha. There was no marked difference in MTA1 and ER-alpha expression levels between HCC cell line expressing wild-type p53 and cell line with mutated p53 HCC. In conclusion, these findings indicate that overexpression of MTA1 is associated with HCC growth and vascular invasion. Nuclear translocation of ER-alpha inversely correlated with MTA1 expression, suggesting negative regulatory mechanisms.
Moon
Woo Sung
WS
Department of Medicine, Veterans Administration Medical Center, Long Beach, California, USA.
Chang
Kenneth
K
Tarnawski
Andrzej S
AS
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53