At present, it would be difficult to correlate the increased VEGFR1 surface levels to increased second messenger signaling, as VEGFR1 signals through the PI3K/Akt and phospholipase C gamma/protein kinase C pathways 98, which are constitutively active in breast cancer cell lines, xenografts, and tissue 66,99–102. This evidence concerns the gene AKT1 and breast cancer.