Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Contributes to Tamoxifen Resistance in Estrogen-Positive Breast Cancer Patients

Crosstalk between the estrogen receptors and the receptor tyrosine kinases, including vascular endothelial growth factor receptor type II (VEGFR2), is a key mechanism in breast cancer resistance to antiestrogen therapy with tamoxifen. A high level of VEGFR2 expression in a tumor serves as a marker o...

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Bibliographic Details
Published in:Molecular biology (New York) 2021, Vol.55 (1), p.102-108
Main Authors: Dronova, T. A., Babyshkina, N. N., Zavyalova, M. V., Slonimskaya, E. M., Cherdyntseva, N. V.
Format: Article
Language:English
Subjects:
Antiestrogens
Biochemistry
Biomedical and Life Sciences
Breast cancer
Estrogen receptors
Estrogens
Gene expression
Human Genetics
Immunohistochemistry
KDR gene
Kinases
Life Sciences
Metastases
Molecular Cell Biology
Phenotypes
Single-nucleotide polymorphism
Tamoxifen
Tyrosine
Vascular endothelial growth factor
Vascular endothelial growth factor receptor 2
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Summary:Crosstalk between the estrogen receptors and the receptor tyrosine kinases, including vascular endothelial growth factor receptor type II (VEGFR2), is a key mechanism in breast cancer resistance to antiestrogen therapy with tamoxifen. A high level of VEGFR2 expression in a tumor serves as a marker of tamoxifen resistance. The tamoxifen efficacy prognostic value of functional polymorphisms in the VEGFR2 / KDR gene has not been established. Using qRT-PCR, we detected the rs2071559 and the rs2305948 variants and the levels of KDR gene expression in 122 breast tumor tissue samples from cohorts of patients with progression (distant metastases or relapse) and patients with no progression during tamoxifen therapy. The expression levels of VEGFR2 protein were analyzed by immunohistochemistry. The frequency of heterozygous and mutant genotypes of the rs2305948 SNP was significantly higher in patients without progression than in the cohort with progression. KDR rs2305948 was associated with high survival rates in breast cancer patients. A correlation between the mRNA of the ESR1 and KDR genes in patients without progression was detected. The results indicate the prognostic value of rs2305948 and its potential contribution to the tumor phenotype sensitive to tamoxifen.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893321010052