Helicobacter pyloriActivates the Cyclin D1 Gene through Mitogen- Activated Protein Kinase Pathway in Gastric Cancer Cells
- 1 June 2001
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 69 (6), 3965-3971
- https://doi.org/10.1128/iai.69.6.3965-3971.2001
Abstract
Helicobacter pylori induces cellular proliferation in host cells, but the mechanism remains unclear. Thus, we examined the effect of H. pylori on cyclin D1, an important regulator of the cell cycle, especially in relation to intracellular signaling pathways. In a Northern blot analysis, cyclin D1 transcription in gastric cancer (AGS) cells was enhanced by coculture with H. pylori strain TN2 in a time-dependent and multiplicity-of-infection-dependent manner. An isogenic mutant form ofvacA also increased cyclin D1 transcription, but mutant forms of cagE or the entire cag pathogenicity island did not enhance cyclin D1 transcription. These effects were confirmed with a luciferase assay of the cyclin D1 promoter (pD1luc). Cyclin D1 promoter activation by H. pylori was inhibited by MEK inhibitors (U0126 and PD98059), indicating that the mitogen-activated protein kinase pathway may be involved in intracellular signal transduction. In contrast, transfection of a reporter plasmid having any point mutations of the NF-κB binding sites in the promoter (pD1-κB1M, pD1-κB2M, or pD1-κB1/2M) or cotransfection of dominant negative IκBα did not affect cyclin D1 activation by H. pylori. In conclusion, H. pylori activates cyclin D1 through the mitogen-activated protein kinase pathway and not through NF-κB activation in AGS cells. This activation of cyclin D1 is partly dependent on the cagpathogenicity island but not on vacA.Keywords
This publication has 59 references indexed in Scilit:
- Helicobacter pylori induced transactivation of SRE and AP-1 through the ERK signalling pathway in gastric cancer cellsGut, 2001
- Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV SecretionScience, 2000
- IκBα Ubiquitination Is Catalyzed by an SCF-like Complex Containing Skp1, Cullin-1, and Two F-Box/WD40-Repeat Proteins, βTrCP1 and βTrCP2Biochemical and Biophysical Research Communications, 1999
- Cancer Cell CyclesScience, 1996
- Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesisGastroenterology, 1996
- Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesionsNature Medicine, 1995
- Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic miceNature, 1994
- Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa.Journal of Clinical Pathology, 1994
- Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts.Genes & Development, 1993
- A novel cyclin encoded by a bcl1-linked candidate oncogeneNature, 1991