Mammary tumor growth and pulmonary metastasis are enhanced in a hyperlipidemic mouse model

摘要: Dyslipidemia has been associated with an increased risk for developing cancer. However, the implicated mechanisms are largely unknown. To explore role of dyslipidemia in breast cancer growth and metastasis, we used apolipoprotein E (ApoE) knockout mice (ApoE(-/-)), which exhibit marked dyslipidemia, elevated circulating cholesterol triglyceride levels setting normal glucose homeostasis insulin sensitivity. Non-metastatic Met-1 metastatic Mvt-1 mammary cells derived from MMTV-PyVmT/FVB-N transgenic c-Myc/vegf tumor explants respectively, were injected into fat pad ApoE(-/-) wild-type (WT) females consuming a high-fat/high-cholesterol diet was evaluated. exhibited displayed greater number spontaneous metastases to lungs. Furthermore, intravenous injection resulted pulmonary lungs compared WT controls. unravel molecular mechanism involved enhanced mice, studied response vitro. We found that Akt(S473) phosphorylation as well cellular proliferation, whereas depletion cell membrane abrogated induced by exogenously added cholesterol. vivo administration BKM120, small-molecule inhibitor phosphatidylinositol 3-kinase (PI3K), alleviated dyslipidemia-induced metastasis model concomitant decrease PI3K/Akt signaling. Collectively, suggest hypercholesterolemic milieu is favorable metastasis.