Overexpression of extracellular signal-regulated protein kinase and its correlation with proliferation in human hepatocellular carcinoma.
BACKGROUND
Dysregulation of cell proliferation is one of the most important features of human cancers including hepatocellular carcinoma (HCC). However, the molecular basis underlying the proliferation of HCC has not been fully clarified. Because a previous study reported that overexpression of extracellular signal-regulated protein kinase (ERK), which transduces extracellular growth stimuli to the nuclei, was frequently observed in several human cancers, this study was performed to analyze the expression of ERK in human HCC and its correlation with HCC proliferation.


METHODS
Twenty-four paired samples of primary HCCs and corresponding noncancerous liver tissues, and six samples of histologically normal liver tissue were obtained from surgically resected materials. The expression of ERK was examined by immunoblotting and immunohistochemical analysis. Proliferative activity of each HCC was examined by immunohistochemical demonstration of proliferative cell nuclear antigen (PCNA).


RESULTS
The ERK1 and ERK2 expression in HCCs was significantly higher than that in noncancerous liver tissues, and the ERK1 expression in noncancerous liver tissues from patients with HCC was higher than that in tissue from normal liver. Immunohistochemical examination revealed enhanced accumulation of ERK1 in the nuclei of HCC cells. Regression analysis revealed a significant correlation between ERK expression and PCNA labeling index in HCC.


CONCLUSIONS
Our findings suggest that ERK overexpression contributes to the proliferation of HCC.
Divison of Gastroenterology and Hepatology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Yasunori
Y
Tsuboi
Takafumi
T
Ichida
Soichi
S
Sugitani
Takuya
T
Genda
Jun
J
Inayoshi
Masaaki
M
Takamura
Yasunobu
Y
Matsuda
Minoru
M
Nomoto
Yutaka
Y
Aoyagi
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3