BST-2/tetherin is overexpressed in mammary gland and tumor tissues in MMTV-induced mammary cancer

Abstract

BST-2 restricts MMTV replication, but once infection has established, MMTV modulates BST-2 levels. MMTV-directed BST-2 modulation is tissue-specific and dependent on infection and neoplastic transformation status of cells. In the lymphoid compartment of infected mice, BST-2 expression is first upregulated and then significantly downregulated regardless of absence or presence of mammary tumors. However, in mammary gland tissues, upregulation of BST-2 expression is dependent on the presence of mammary tumors and tumor tissues themselves have high BST-2 levels. Elevated BST-2 expression in these tissues is not attributable to IFN since levels of IFNα and IFNγ negatively correlate with BST-2. Importantly, soluble factors released by tumor cells suppress IFNα and IFNγ but induce BST-2. These data suggest that overexpression of BST-2 in carcinoma tissues could not be attributed to IFNs but to a yet to be determined factor that upregulates BST-2 once oncogenesis is initiated.

Keywords: AKT; BST-2; Bone marrow stromal cell antigen 2; CCL3; Cancer; Epithelial cells; FACS; Fluorescence activated cell sorting; Human breast cancer; MIP1-α/CCL3; MIP1α; Macrophage inflammatory protein 1-alpha; Mammary gland; Mouse mammary tumor virus; NMuMG; Normal murine mammary gland; PI3K; Phosphoinositide 3 kinase; Tetherin; Transformation; Tumor.