Figure 6

Apoptosis, cell proliferation, lymphatic vessels with intraluminal tumor cells and ERα expression in mammary carcinomas. Whereas some TUNEL-positive cells are seen in the tumor of a control mouse (A), many more TUNEL-positive cells are observed in the tumor of a mouse given 27 mg/kg raloxifene (B). ×200. Expression of active caspase-3 (C and D, x200)and caspase-9 (E and F, x400) was more prominent in the tumor of a mouse given 27 mg/kg raloxifene (D and F) than in a control mouse (C and E). The number of BrdU-labeled cells tended to be lower in the 27 mg/kg raloxifene group (H) than in the control group (G). ×200. Podoplanin-positive lymphatic vessels of a tumor in a control mouse were often dilated and filled with tumor cells (arrows, I). Raloxifene-treated groups showed a significant reduction in the numbers of dilated lymphatic vessels containing intraluminal tumor cells. (arrows, J). ×200. The nuclear ERα expression of adjacent normal mammary glands in the mammary tumor was much stronger in the control (K) than in the 27 mg/kg raloxifene group (L). ×400. The scattered expression of cytoplasmic ERα was much stronger in the control group (M) than in the 27 mg/kg raloxifene group (N). ×400. A and B, TUNEL stain; C and D, active caspase-3 immunohistochemistry; E and F, active caspase-9 immunohistochemistry; G and H, BrdU immunohistochemistry; I and J, podoplanin immunohistochemistry. K-N, ERα immunohistochemistry.