Junctional adhesion molecule-A promotes proliferation and inhibits apoptosis of gastric cancer.
OBJECTIVE
Junctional adhesion molecules (JAMs) are known as integral constituents of cellular tight junctions. However, the functions of JAMs in cancer tissues are controversial and the function of JAM-A in gastric cancer is unclear. Acordingly, we investigated the function of JAM-A in gastric epithelial and gastric cancer cell proliferation, invasion and apoptosis.


METHODS
A normal rat gastric mucosa-derived cell line (RGM1), a rat gastric cancer-like cell line established from RGM1 (RGK1), and a human gastric cancer cell line (NCI-N87) were used in this study. To examine the expression of junctional proteins, immunoblotting and immunofluorescent staining were performed with specific antibodies (JAM-A, claudins, occludin and ZO-1). JAM-A was knocked down by small interfering RNA.


RESULTS
RGM1 and RGK1 expressed JAM-A, occludin and ZO-1 but not claudins. RGK1 were significantly more invasive than RGM1. JAM-A knock-down significantly decreased the proliferation and the invasion of RGK1 but not of RGM1. JAM-A knock-down significantly decreased the proliferation of NCI-N87 cells and significantly decreased expression of the anti-apoptotic protein Bcl-xL but not the expression of AKT or Mcl-1.


CONCLUSIONS
JAM-A promotes proliferation and inhibits apoptosis of gastric cancer, suggesting that it has a pivotal role in gastric cancer progression.
Koichi
K
Ikeo
Tadayuki
T
Oshima
Jing
J
Shan
Hirofumi
H
Matsui
Toshihiko
T
Tomita
Hirokazu
H
Fukui
Jiro
J
Watari
Hiroto
H
Miwa
D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D057167:Claudins / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D062793:Occludin / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494811:BCL2L1 protein, human; D015815:Cell Adhesion Molecules; D057167:Claudins; C407243:F11R protein, human; D062793:Occludin; C568987:Ocln protein, rat; D011956:Receptors, Cell Surface; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D051020:bcl-X Protein