Frequent activation of mitogen-activated protein kinase relative to Akt in extrahepatic biliary tract cancer.
BACKGROUND
Lack of effective adjuvant therapy against advanced extrahepatic biliary tract carcinoma (BTC) requires that new therapeutic methods, such as molecular targeted therapy, be developed. The mitogen-activated protein kinase (MAPK) and Akt signaling pathways, which activate cell proliferation and suppress apoptosis, respectively, may function as important targets for such therapies. The aim of this study was to examine the expression patterns of phosphorylated MAPK (p-MAPK) and phosphorylated Akt (p-Akt) proteins in BTC cell lines and clinical specimens.


METHODS
Expression of p-MAPK and p-Akt proteins in four human BTC cell lines and in frozen sections of 20 advanced extrahepatic BTC specimens was analyzed by Western blotting. Thirty formalin-fixed BTC specimens were immunohistochemically stained for p-MAPK and p-Akt using labeled streptavidin-biotin conjugates.


RESULTS
Expression of p-MAPK was observed in three of four (75%) BTC cell lines, whereas no expression of p-Akt was observed. Twenty-three of 30 formalin-fixed specimens stained positive for p-MAPK (77%), whereas only 47% stained positively for p-Akt. Expression of p-MAPK relative to that of p-Akt was also seen more frequently in the frozen specimens.


CONCLUSIONS
The results of this study suggest that MAPK is activated more frequently than Akt in extrahepatic biliary tract carcinoma.
Hori
Hiroshige
H
Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Ajiki
Tetsuo
T
Mita
Yoshiyasu
Y
Horiuchi
Hideki
H
Hirata
Kenro
K
Matsumoto
Taku
T
Morimoto
Haruki
H
Fujita
Tsunenori
T
Ku
Yonson
Y
Kuroda
Yoshikazu
Y
D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases