title: c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, Chiyoda-ku, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Shibata
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Yohko
authors.initials: Y
authors.lastname: Hikiba
authors.forename: Ayako
authors.initials: A
authors.lastname: Yanai
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Ogura
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: 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
chemical_list: D008770:Methylnitrosourea; D048055:Mitogen-Activated Protein Kinase 8