Increased tumor latency and decreased metastasis in oncogene induced mammary tumors from SRC-1 null mutant mice. (A) Mammary tumor formation (at left) in the MMTV-neu mouse. (B, C) The histopathologic appearance of mammary tumors from the SRC1-/-;neu mouse resembles poorly differentiated adenocarcinoma in humans. Hematoxylin and eosin stained sections are shown. Scale bars 100 μm and 50 μm respectively. (D) Histopathologic appearance of human poorly differentiated adenocarcinoma stained with hematoxylin and eosin. Scale bar = 50 μm. (E, F) Histopathologic appearance of early mammary tumors (prior to detection by palpation) in SRC1+/+;neu and SRC1-/-;neu mice is consistent with poorly differentiated adenocarcinoma. Scale bar = 100 μm. (G, H) Histopathologic appearance of SRC1+/+;neu and SRC1-/-;neu mammary tumor lung metastases is consistent with poorly differentiated adenocarcinoma. Scale bars = 50 μm. (I) Increased tumor latency in SRC1-/-;neu mice compared to SRC1+/+;neu animals. Mice of both genotypes were treated with AGN194204 (AGN), clofibrate (clo), or ciglitazone (cig) as described in Materials and Methods. The mammary gland chains of mice were examined weekly by palpation to detect tumors. (J) Decreased mammary tumor metastasis in SRC1-/- mice. SRC1+/+;neu and SRC1-/-;neu mice were treated with 100 mg/kg AGN194204, clofibrate, or ciglitazone as described in Materials and Methods. The number of metastatic lung lesions was counted at necropsy in each group of mice. (K) Loss of SRC-1 expression inhibits proliferation index in oncogene induced mammary tumors. Tumor sections from SRC1+/+;neu and SRC1-/-;neu were subjected to immunohistochemistry using anti-PCNA antibody. These experiments were performed 3 times with similar results. Representative sections are shown.