Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) in human hepatocellular carcinoma.
One of the major obstacles in the treatment of hepatocellular carcinoma (HCC) is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the expression of ATP7B has not previously been addressed in human liver and HCC. Our purpose was to investigate ATP7B expression in human liver and hepatocellular carcinoma and its clinical significance. We retrospectively examined the expression of ATP7B in primary hepatocellular carcinoma. Immunohistochemical analysis of ATP7B was performed using a monoclonal antibody against ATP7B in 19 surgically removed hepatocellular carcinomas. A variable degree of cytoplasmic staining of tumor cells was observed in 21.1% (4/19) of the analyzed carcinomas. ATP7B expression was not observed in normal hepatic cells. Strong expression of ATP7B was observed in all the analyzed bile ducts. These findings suggest that overexpression of ATP7B in hepatocellular carcinoma might be associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Further, ATP7B is expressed in bile duct epithelial cells, where it may mediate copper secretion into bile fluid.
Sugeno
Hidekazu
H
Department of Surgery II, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan.
Takebayashi
Yuji
Y
Higashimoto
Masashi
M
Ogura
Yoshito
Y
Shibukawa
Goro
G
Kanzaki
Atsuko
A
Terada
Kunihiko
K
Sugiyama
Toshihiro
T
Watanabe
Kumiko
K
Katoh
Ryoji
R
Nitta
Yasutaka
Y
Fukushima
Toshihiko
T
Koyama
Yoshihisa
Y
Inoue
Norio
N
Sekikawa
Kohji
K
Ogawa
Kenji
K
Sato
Yukio
Y
Takenoshita
Seiichi
S
D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001652:Bile Ducts / Q000201:enzymology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology*; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000276:immunology; D002945:Cisplatin / Q000494:pharmacology; D000073840:Copper-Transporting ATPases; D003594:Cytoplasmic Granules / Q000201:enzymology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D012189:Retrospective Studies
D000911:Antibodies, Monoclonal; D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002945:Cisplatin