Figure 7.
Increased chemokine production in FIP200-null tumor cells and a working model. (A) Mammary tumor cells were isolated from Ctrl-MT or CKO-MT mice. RNA was isolated from the purified cells and subjected to analysis by qRT–PCR to detect the expression of various chemokines as indicated. The mean ± SD of relative levels (normalized to Ctrl-MT tumors) from three independent experiments is shown. (*) P < 0.05; (**) P < 0.01. (B,C) Mammary tumor cells from Ctrl-MT or CKO-MT mice (B) and FIP200 KO (FIP200−/−) or control (FIP200f/f) cells (C) were transfected with 10 μg/mL poly(I:C) or mock using Lipofectamine. RNA was isolated at 8 h after stimulation and subjected to qRT–PCR analysis for the relative level of IFN-β (left) and CXCL10 (right). (**) P < 0.01. (D) Mammary tumor cells from Ctrl-MT or CKO-MT mice were stimulated by poly(I:C) for 8 h as described in B. The amount of CXCL10 in the medium was then measured by ELISA using a kit (R & D Systems). (**) P < 0.01. (E) A working model summarizing the potential mechanisms of suppression of mammary tumorigenesis and progression in CKO-MT mice. Inactivation of FIP200 results in defective autophagy in tumor cells that may trigger multiple events leading to the inhibition by mammary tumorigenesis through both reduced cell proliferation and increased immune surveillance in the host.