Expression of the Ets-1 proto-oncogene is linked to cell differentiation of human hepatocellular carcinoma.
OBJECTIVE
Ets-1 regulates the expression of a number of genes related to remodeling of the extracellular matrix. Ets-1 is associated with the occurrence of invasive processes, proliferation and differentiation. Less is known about the biological functions of Ets-1 in human hepatocellular carcinoma. In an attempt at elucidation, we examined immunohistochemically hepatocellular carcinoma followed by application of genetic techniques.


METHODS
We performed immunohistochemical analysis on tissue from 59 Japanese patients undergoing surgical resection of hepatocellular carcinoma using the antibody against human Ets-1. We compared Ets-1 expression in relation to clinicopathological findings. In situ hybridization and reverse transcription-polymerase chain reaction were also performed to confirm the expression of Ets-1 messenger RNA in hepatocellular carcinoma tissues.


RESULTS
In specimens from 59 patients with hepatocellular carcinoma, 41 (70%) showed positive staining for Ets-1 protein. The expression of Ets-1 messenger RNA was also observed in hepatocellular carcinoma tissues by in situ hybridization and reverse transcription-polymerase chain reaction. The expression of Ets-1 correlated with histological differentiation of hepatocellular carcinoma (P < 0.05). Ets-1 was positive in 2 (50%) of the 4 well-differentiated hepatocellular carcinomas and in 28 (64%) of the 44 moderately differentiated hepatocellular carcinomas, whereas all the 11 poorly differentiated hepatocellular carcinomas were positive for Ets-1 staining. Ets-1 protein was expressed more strongly at the peripheral than the central area of the tumor. Otherwise, no particular correlation was evident in terms of clinicopathological factors.


CONCLUSIONS
We found Ets-1 to be expressed in human hepatocellular carcinoma, particularly at the peripheral area of the tumor. As this expression is linked to cell differentiation, this gene may yield biological information relative to this malignant tumor of the liver.
Kanda
Kazuaki
K
Department of Surgery II, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. kanematu@net.nagasaki-u.ac.jp
Nakayama
Toshiyuki
T
Onizuka
Shinya
S
Tomioka
Tsutomu
T
Kanematsu
Takashi
T
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000378:metabolism*; D016016:Proportional Hazards Models; D000090063:Proto-Oncogene Mas; D050783:Proto-Oncogene Proteins c-ets; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
C086924:Elk3 protein, mouse; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors