Helicobacter pylori membrane protein 1: a new carcinogenic factor of Helicobacter pylori
M Suganuma1, M Kurusu, S Okabe
1Saitama Cancer Center, Saitama 362-0806, Japan.
Abstract:
Considering a suspected link between Helicobacter pylori infection and human stomach cancer, a new H. pylori gene for membrane protein 1 (HP-MP1) was recently cloned. Because HP-MP1 induces release of inflammatory cytokines and tumor necrosis factor-alpha acts as both initiator and tumor promoter, we studied the possible involvement of HP-MP1 in carcinogenesis of H. pylori. Two cell lines, BALB/3T3 cells as control and v-Ha-ras-transfected BALB/3T3 cells (Bhas 42 cells) as putative initiated cells, were each transfected with HP-MP1, urease B genes, or vector alone. All of the Bhas/mpl clones showed strong expression of tumor necrosis factor-alpha gene and produced tumors in 100% of nude mice. Two Bhas/ure clones showed weak tumorigenicity; the other Bhas and BALB clones showed none. Results indicate strong carcinogenic activity of HP-MP1 in cooperation with viral Ras protein and weak activity of urease B.
Insights
Helicobacter pylori membrane protein 1 (HP-MP1) shows strong carcinogenic activity. HP-MP1 cooperates with viral Ras protein, promoting stomach cancer development.
Area of Science:
- Microbiology
- Oncology
- Molecular Biology
Background:
- Helicobacter pylori infection is linked to human stomach cancer.
- A novel H. pylori gene, membrane protein 1 (HP-MP1), induces inflammatory cytokines.
- Tumor necrosis factor-alpha (TNF-α) is implicated in cancer initiation and promotion.
Purpose of the Study:
- To investigate the role of HP-MP1 in H. pylori-associated carcinogenesis.
- To determine the carcinogenic potential of HP-MP1 and urease B genes in specific cell lines.
Main Methods:
- Transfection of BALB/3T3 (control) and Bhas 42 (initiated) cells with HP-MP1, urease B, or vector DNA.
- Assessment of TNF-α gene expression.
- Tumorigenicity testing in nude mice.
Main Results:
- Bhas 42 cells transfected with HP-MP1 (Bhas/mpl clones) exhibited strong TNF-α expression and 100% tumor formation in nude mice.
- Bhas 42 cells transfected with urease B (Bhas/ure clones) showed weak tumorigenicity.
- Control BALB/3T3 cells and vector-transfected cells did not form tumors.
Conclusions:
- HP-MP1 demonstrates significant carcinogenic activity, particularly in cooperation with viral Ras protein.
- Urease B exhibits weak carcinogenic activity.
- HP-MP1 is a key factor in H. pylori-induced stomach carcinogenesis.
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