Overexpression of extracellular signal‐regulated protein kinase and its correlation with proliferation in human hepatocellular carcinoma

Liver International - Tập 24 Số 5 - Trang 432-436 - 2004
Yasunori Tsuboi1, Takafumi Ichida1, Soichi Sugitani2, Takuya Genda1, Jun Inayoshi1, Masaaki Takamura1, Yasunobu Matsuda1, Minoru Nomoto1, Yutaka Aoyagi1
1Divison of Gastroenterology and Hepatology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
2Department of Internal Medicine, School of Dentistry at Niigata, The Nippon Dental University, Niigata, Japan

Tóm tắt

Abstract: 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.

Từ khóa


Tài liệu tham khảo

10.1016/S0168-8278(98)80355-3

10.1111/j.1349-7006.1990.tb02525.x

10.1002/hep.510230535

Adachi T, 1996, Mitogen‐activated protein kinase activation in hepatocyte growth factor‐stimulated rat hepatocytes, involvement of protein tyrosine kinase and protein kinase C, 23, 1244

10.1016/0092-8674(94)90133-3

10.1126/science.8052857

10.1172/JCI119309

Mishima K, 1998, Overexpression of the ERK/MAP kinases in oral squamous cell carcinoma, Mod pathol, 11, 886

10.1002/hep.510260615

Sato Y, 1986, The Amex method. A simplified technique of tissue processing and paraffin embedding with improved preservation of antigens for immunostaining, Am J Pathol, 125, 431

10.1016/0016-5085(95)90450-6

Hall P A, 1990, Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections, an index of cell proliferation with evidence of deregulated expression in some neoplasms, 162, 285

10.1006/bbrc.1997.6840

Fukuda M, 1997, Interaction of MAP kinase with MAP kinase kinase, its possible role in the control of nucleocytoplasmic transport of MAP kinase, 16, 1901

10.1083/jcb.122.5.1079

10.1038/sj.bjc.6601644

10.1002/hep.510270409

10.1016/S0022-5347(05)68354-1

Thông tin
Thông tin xuất bản

Liver International

Tập 24 Số 5

432-436

Thông tin tác giả