title: Overexpression of cyclin DI contributes to malignant properties of esophageal tumor cells by increasing VEGF production and decreasing Fas expression.
abstract: Cyclin D1 is frequently overexpressed in human esophageal cancer. We examined the possible role of cyclin D1 overexpression on specific malignant properties of tumor cells using a series of eight human esophageal cancer cell lines that express different levels of cyclin D1. We did not find a simple correlation between levels of cyclin D1 expression and anchorage-independent growth, production of angiogenic factors, or tumorigenicity in nude mice, suggesting that other factors can influence these parameters. We did, however, obtain evidence that tumorigenicity appeared to require both the capacity for anchorage-independent growth and the production of angiogenic factors. To better assess the specific role of cyclin D1, we stably expressed an antisense cyclin D1 cDNA construct in the tumorigenic cell line TTn. This significantly decreased anchorage-independent growth and VEGF production and led to a loss of tumorigenicity in nude mice. Furthermore, these cells diplayed a marked increase in sensitivity to antitumor agents and to Fas antibody-induced apoptosis. Taken together, these findings suggest that the overexpression of cyclin D1 can confer esophageal cancer cells with enhanced malignancy through increases in anchorage-independent growth and VEGF production, and down-regulation of Fas expression, thus suggesting novel functions of the cyclin D1 protein in tumor progression.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors.forename: Masafum
authors.initials: M
authors.lastname: Shintani
authors.forename: Aki
authors.initials: A
authors.lastname: Okazaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuda
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ishizuka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: I Bernard
authors.initials: IB
authors.lastname: Weinstein
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016373:DNA, Antisense / Q000096:biosynthesis / Q000235:genetics; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: D016373:DNA, Antisense; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019014:fas Receptor; D019938:Cyclin D1