Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

摘要: Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors poor prognosis. However, the precise role of CYP4Z1 tumor progression unknown. Here, we demonstrate that overexpression promotes angiogenesis growth breast cancer. Stable expression T47D BT-474 cancer cells significantly increased mRNA production vascular endothelial factor (VEGF)-A, decreased levels secretion tissue inhibitor metalloproteinase-2 (TIMP-2), without affecting cell proliferation anchorage-independent vitro. Notably, conditioned medium from CYP4Z1-expressing enhanced proliferation, migration tube formation umbilical vein cells, promoted zebrafish embryo chorioallantoic membrane chick embryo. In addition, there were lower myristic acid lauric acid, higher contents 20-hydroxyeicosatetraenoic (20-HETE) compared vector control. weight microvessel density by 2.6-fold 1.9-fold xenograft models, respectively. Moreover, transfection phosphorylation ERK1/2 PI3K/Akt, while PI3K or ERK inhibitors siRNA silencing reversed CYP4Z1-mediated changes VEGF-A TIMP-2 expression. Conversely, HET0016, an family, potently inhibited tumor-induced intracellular 20-HETE. Collectively, these data suggest partly via PI3K/Akt activation.