Vascular endothelial growth factor polymorphisms affect gene expression and tumor aggressiveness in patients with breast cancer

Sa-Nguanraksa,Doonyapat; Kooptiwut,Suwattanee; Chuangsuwanich,Tuenjai; Pongpruttipan,Tawatchai; Malasit,Prida; O-Charoenrat,Pornchai

doi:10.3892/mmr.2014.1890

Vascular endothelial growth factor polymorphisms affect gene expression and tumor aggressiveness in patients with breast cancer

Authors:
- Doonyapat Sa-Nguanraksa
- Suwattanee Kooptiwut
- Tuenjai Chuangsuwanich
- Tawatchai Pongpruttipan
- Prida Malasit
- Pornchai O-Charoenrat
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Affiliations: Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Division of Head-Neck and Breast Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Published online on: January 9, 2014 https://doi.org/10.3892/mmr.2014.1890
Pages: 1044-1048

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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 -1498T/-634C haplotype exhibited the highest basal promoter activity. These findings suggest that the interaction between -1498T and -634C polymorphisms increases VEGF expression and is involved in breast cancer aggressiveness.

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