Involvement of the mitogen-activated protein kinase kinase 2 in the induction of cell dissociation in pancreatic cancer.
In our previous investigation, mitogen-activated protein kinase kinase 2 (MEK2) was detected as a factor which was correlated to the potential of invasion-metastasis. In this study, the immunocytochemical, immunohistochemical and mRNA expressions of MEK2 were examined in pancreatic cancer cell lines and tissue samples, respectively. Constitutive expressions of MEK2 and phosphorylated MEK (p-MEK) were observed in PC-1.0 and ASPC-1 cells, which exhibited a growth pattern of single cells, whereas the relevant expressions were quite faint in PC-1 cells and CAPAN-2 cells, which exhibited a growth pattern of island-like clonies. Simultaneous inductions of MEK2 expressions and cell dissociation were observed after the treatment with a conditioned medium (CM) of PC-1.0 cells. The expression of MEK2 and p-MEK were reduced and the cell aggregation was found in PC-1.0 and ASPC-1 cells after U0126 (a MEK inhibitor) treatment. In vivo, both the MEK2 and p-MEK overexpressed in human pancreatic cancer tissues and p-MEK was found to be more strongly expressed in the invasive front than that in the center of tumor (P<0.05). MEK2 is closely related to pancreatic cancer cell dissociation. MEK2 activation is probably involved in the first step of the cascade in the invasion-metastasis of pancreatic cancer.
Tan
Xiaodong
X
Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan.
Egami
Hiroshi
H
Kamohara
Hidenobu
H
Ishikawa
Shinji
S
Kurizaki
Takashi
T
Yoshida
Naoya
N
Tamori
Yasuhiko
Y
Takai
Eiji
E
Hirota
Masahiko
M
Ogawa
Michio
M
D000328:Adult; D000368:Aged; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D048370:MAP Kinase Kinase 2; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D002070:Butadienes; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D009570:Nitriles; D012333:RNA, Messenger; C113580:U 0126; C482128:MAP2K2 protein, human; D011505:Protein-Tyrosine Kinases; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases