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VEGF, estrogen, and ER status in breast cancer

Estrogen is correlated with increased VEGF expression7

Estrogen is correlated with increased VEGF expression
Buteau-Lozano et al showed that VEGF expression, as measured by protein levels, increased with the addition of estrogen to breast tumor cell lines. This chart depicts VEGF protein levels over time in 2 breast cancer cell lines (MCF-7, open symbols; MDA-MB-231, closed symbols) untreated with estrogen (controls, round symbols) or treated with various levels of estrogen (1 nM, square symbols; 10 nM, triangular symbol).7

Reprinted with permission of the American Association for Cancer Research. Buteau-Lozano H, Ancelin M, Lardeux B, et al. Cancer Res. 2002;62:4977-4984.

Results from a number of studies indicate that expression of growth factors, such as vascular endothelial growth factor (VEGF), can be regulated by hormones via direct (autocrine) and indirect (paracrine) mechanisms. One example is the relationship between estrogen and VEGF expression in breast cancer. Buteau-Lozano and colleagues confirmed, in preclinical models, that estrogen modulates VEGF expression at the gene transcriptional level in breast cancer cells, suggesting a complex relationship between estrogen and VEGF expression. Additional research suggests that VEGF expression in estrogen-dependent breast cancers contributes to both angiogenesis and estrogen-independent growth.7 Furthermore, VEGF levels have also been associated with response to anti-estrogen therapy in adjuvant treatment of estrogen receptor (ER)–positive breast cancer.5

The work of Buteau-Lozano and colleagues showed that the hormone estrogen increased VEGF production. However, the receptor for estrogen may have a different relationship with VEGF, as shown in a 2006 study. Fuckar and colleagues reported the results of a study of 233 breast cancer specimens investigating the relationship between VEGF, hormone receptor status, and other variables. In this study, VEGF expression significantly correlated with ER-negative status. Note that ER-negative breast cancers are associated with a poorer prognosis than ER-positive breast cancers.8

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