Zonula occludens-1 (ZO-1) redistribution is involved in the regulation of cell dissociation in pancreatic cancer cells.
In our previous study, dissociation factor (DF) and mitogen-activated protein kinase kinase 2 (MEK2) were isolated as factors relating to cancer cell dissociation in pancreatic cancer cells. On the other hand, tight junction protein zonula occludens 1 (ZO-1) has been indicated to be involved in carcinogenesis. In this study, the expression of ZO-1 and a downstream kinase of MEK2, extracellular signal-regulated kinase 2 (ERK2), was analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and two human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines were used. Immunocytochemical study was performed using anti-ZO-1, ERK2, and phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF treatment obviously disrupted ZO-1 expression at the sites of cell-cell contact and markedly induced ERK2 and p-ERK1/2 expression, as well as the dissociation of cell clones in PC-1 and CAPAN-2 cells. In contrast, U0126 (a MEK1/2 inhibitor) treatment significantly induced the peripheral distribution of ZO-1 as well as cell aggregation in PC-1.0 and AsPC-1 cells, which usually grew as single cells, but seriously suppressed ERK2 and p-ERK1/2 expression. We conclude that redistribution of ZO-1 is closely correlated with cell dissociation status in pancreatic cancer cells through activation of ERK2.
Tan
Xiaodong
X
Department of Surgery II, Kumamoto University Medical School, Honjo, Kumamoto, Japan. tanxd@hotmail.com
Egami
Hiroshi
H
Ishikawa
Shinji
S
Kurizaki
Takashi
T
Hirota
Masahiko
M
Ogawa
Michio
M
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D019950:Mitogen-Activated Protein Kinase 1