title: Vascular endothelial growth factor polymorphisms affect gene expression and tumor aggressiveness in patients with breast cancer.
abstract: Vascular endothelial growth factor (VEGF) is one of the key modulators of angiogenesis. The highly polymorphic promoter and 5' untranslated region of VEGF have been associated with susceptibility to and aggressiveness of several types of cancer. To examine the functional role of VEGF polymorphisms at -634 and -1498 positions, VEGF mRNA and protein in breast cancer tissues were analyzed by quantitative polymerase chain reaction and immunohistochemistry. A dual-luciferase assay was performed to determine promoter activity. The VEGF-634CC genotype demonstrated the highest VEGF mRNA expression. High VEGF mRNA expression was correlated with a tumor size of >2 cm, the presence of lymphovascular invasion and the presence of axillary nodal metastasis. The promoter containing the -1,498T/-634C haplotype exhibited the highest basal promoter activity. These findings suggest that the interaction between -1,498T and -634C polymorphisms increases VEGF expression and is involved in breast cancer aggressiveness.
authors.affiliation: Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Doonyapat
authors.initials: D
authors.lastname: Sa-Nguanraksa
authors.affiliation: Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Suwattanee
authors.initials: S
authors.lastname: Kooptiwut
authors.affiliation: Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Tuenjai
authors.initials: T
authors.lastname: Chuangsuwanich
authors.affiliation: Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Tawatchai
authors.initials: T
authors.lastname: Pongpruttipan
authors.affiliation: Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.affiliation: Division of Head-Neck and Breast Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Pornchai
authors.initials: P
authors.lastname: O-Charoenrat
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D017930:Genes, Reporter; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D016297:Mutagenesis, Site-Directed; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A