Data from Effect of Conditional Knockout of the Type II <i>TGF-β</i> Receptor Gene in Mammary Epithelia on Mammary Gland Development and Polyomavirus Middle T Antigen Induced Tumor Formation and Metastasis

Abstract

<div>Abstract<p>Transforming growth factor–β (TGF-β) isoforms are growth factors that function physiologically to regulate development, cellular proliferation, and immune responses. The role of TGF-β signaling in mammary tumorigenesis is complex, as TGF-β has been reported to function as both a tumor suppressor and tumor promoter. To elucidate the role of TGF-β signaling in mammary gland development, tumorigenesis, and metastasis, the gene encoding type II TGF-β receptor, <i>Tgfbr2</i>, was conditionally deleted in the mammary epithelium (Tgfbr2<sup>MGKO</sup>). Loss of <i>Tgfbr2</i> in the mammary epithelium results in lobular-alveolar hyperplasia in the developing mammary gland and increased apoptosis. Tgfbr2<sup>MGKO</sup> mice were mated to the mouse mammary tumor virus-polyomavirus middle T antigen (PyVmT) transgenic mouse model of metastatic breast cancer. Loss of <i>Tgfbr2</i> in the context of PyVmT expression results in a shortened median tumor latency and an increased formation of pulmonary metastases. Thus, our studies support a tumor-suppressive role for epithelial TGF-β signaling in mammary gland tumorigenesis and show that pulmonary metastases can occur and are even enhanced in the absence of TGF-β signaling in the carcinoma cells.</p></div>