Increased expression of interleukin-1alpha and cyclooxygenase-2 in human gastric cancer: a possible role in tumor progression.
BACKGROUND
Cyclooxygenase (COX)-2 mRNA and protein expression have been found to be frequently up-regulated in human gastric cancers and cell lines. COX-2 is the inducible form of COX, and interleukin (IL)-1alpha may be one of the stimulators of COX-2.


METHODS
The relationship between IL-1alpha and COX-2 expression was examined in human gastric cancer tissues and cell lines.


RESULTS
IL-1alpha mRNA was expressed in 19 out of 32 human gastric cancer specimens (60%), while it was not expressed in any of the paired normal gastric mucosa specimens. The incidence of IL-1alpha mRNA expression was significantly higher in patients with pT2-pT4 tumors than in those with pT1 tumors (86% vs. 39%, p<0.05). IL-1alpha mRNA was expressed in 94% of COX-2-positive tumors, while it was expressed in only 25% of COX-2-negative tumors (p<0.0001). When IL-1alpha was added to the medium of gastric cancer cell lines (MKN28 and MKN45), it enhanced the expression of IL-1alpha itself and COX-2 mRNA in both cell lines. Exogenous IL-1alpha stimulated cancer cell growth in both cell lines, while such growth stimulation was suppressed by anti-IL-1alpha antibody or IL-1 receptor antagonist. IL-1alpha-stimulated cell growth was also suppressed by anti-COX-2 antibody.


CONCLUSIONS
Our data demonstrated that IL-1alpha and COX-2 mRNA were frequently co-expressed in human gastric cancer tissues, and suggested that the IL-1alpha-COX-2 pathway might be involved in tumor progression by regulating cancer cell proliferation.
Uefuji
Kazuhiko
K
Self Defense Force Fukuoka Hospital, 1-61 Kokurahigashi, Kasuga, Fukuoka 816-0826, Japan. k2uefu@med.email.ne.jp
Ichikura
Takashi
T
Mochizuki
Hidetaka
H
D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D018450:Disease Progression; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases