Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer.
Helicobacter pylori (HP) infection is usually accompanied by an increased plasma level of gastrin, a potent mitogen able to induce cyclooxygenase (COX)-2. This study examined (a) the seroprevalence of HP, its cytotoxic protein, CagA, and cytokines (tumor necrosis factor alpha, interleukins 1beta and 8) in 80 patients with colorectal cancers, before and after the removal of tumor, compared with 160 age- and gender-matched controls; (b) the gene expression of gastrin and its receptors (CCKB-R) in the cancer tissue, (c) the plasma levels and tumor tissue contents of gastrin, and (d) the mRNA expression of COX-1, COX-2, and apoptotic proteins (Bax and Bcl2) in cancer tissue and intact colonic mucosa. Anti-HP IgG, anti-CagA IgG seroprevalence, and cytokine levels were analyzed by enzyme-linked immunosorbent assay tests; gene expressions of gastrin, CCKB-R, COX-1, COX-2, Bax, and Bcl2 by reverse transcriptase polymerase chain reaction; and gastrin by radioimmunoassay. The seroprevalence of HP, especially that expressing CagA, was significantly higher in cancer patients than in controls and did not change 1 week after tumor resection while plasma cytokines were significantly reduced after this operation. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and the resection margin; similarly, COX-2 mRNA was expressed in most of cancers and their resection margin but not in intact colonic mucosa, where only COX-1 was detected. The colorectal cancer tissue contained several folds more immunoreactive gastrin than cancer resection margin and many folds more than the intact colonic mucosa. We conclude that colon adenocarcinoma and its resection margin overexpress gastrin, its receptors, CCKB-R, and COX-2, and that HP infection may contribute to colonic cancerogenesis via overexpression of gastrin and COX-2, which may account for the stimulation of the tumor growth and the reduction in apoptosis as documented by enhanced mRNA expression of anti-apoptotic Bcl2 over proapoptotic Bax proteins.
Hartwich
A
A
Department of Surgery, District Hospital, Cracow, Poland.
Konturek
S J
SJ
Pierzchalski
P
P
Zuchowicz
M
M
Labza
H
H
Konturek
P C
PC
Karczewska
E
E
Bielanski
W
W
Marlicz
K
K
Starzynska
T
T
Lawniczak
M
M
Hahn
E G
EG
D000230:Adenocarcinoma / Q000097:blood / Q000382:microbiology*; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial; D017209:Apoptosis; D001426:Bacterial Proteins / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000382:microbiology*; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000097:blood; D005260:Female; D005755:Gastrins / Q000097:blood*; D015870:Gene Expression; D016481:Helicobacter Infections / Q000097:blood / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007527:Isoenzymes / Q000097:blood*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D005755:Gastrins; D007375:Interleukin-1; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C080866:cagA protein, Helicobacter pylori; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases