c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice.
c-Jun NH(2)-terminal kinase (JNK) links several cellular processes, including proliferation and survival, and is believed to be involved in carcinogenesis. However, the role of JNK in gastric tumorigenesis is unknown. Immunohistochemical analysis reveals that JNK is frequently activated in human gastric cancer tissue. We investigated whether JNK1, a major JNK isozyme, is involved in chemically induced gastric cancer development. Mice lacking JNK1 exhibited a marked decrease in gastric carcinogenesis induced by N-methyl-N-nitrosourea, relative to their wild-type counterparts. Impaired tumor development correlated with decreased tumor initiation, which is associated with the production of reactive oxygen species. We also found that lower levels of tumorigenesis were correlated with the decreased expression of cyclin D and CDK as well as decreased cell proliferation. Taken together, JNK seems to be involved in both tumor initiation and promotion and may be an attractive target for the prevention of gastric carcinogenesis.
Shibata
Wataru
W
Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, Chiyoda-ku, Tokyo, Japan.
Maeda
Shin
S
Hikiba
Yohko
Y
Yanai
Ayako
A
Sakamoto
Kei
K
Nakagawa
Hayato
H
Ogura
Keiji
K
Karin
Michael
M
Omata
Masao
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D008770:Methylnitrosourea; D048055:Mitogen-Activated Protein Kinase 8