Supplementary Figure 1 from Effect of Conditional Knockout of the Type II TGF-β Receptor Gene in Mammary Epithelia on Mammary Gland Development and Polyomavirus Middle T Antigen Induced Tumor Formation and Metastasis

Forrester, Elizabeth; Chytil, Anna; Bierie, Brian; Aakre, Mary; Gorska, Agnieszka E.; Sharif-Afshar, Ali-Reza; Muller, William J.; Moses, Harold L.

doi:10.1158/0008-5472.22365333.v1

00085472can043272-sup-can-03-15-05_forrester.pdf (138.98 kB)

Supplementary Figure 1 from Effect of Conditional Knockout of the Type II TGF-β Receptor Gene in Mammary Epithelia on Mammary Gland Development and Polyomavirus Middle T Antigen Induced Tumor Formation and Metastasis

journal contribution

posted on 2023-03-30, 16:48 authored by Elizabeth Forrester, Anna Chytil, Brian Bierie, Mary Aakre, Agnieszka E. Gorska, Ali-Reza Sharif-Afshar, William J. Muller, Harold L. Moses

Supplementary Figure 1 from Effect of Conditional Knockout of the Type II TGF-β Receptor Gene in Mammary Epithelia on Mammary Gland Development and Polyomavirus Middle T Antigen Induced Tumor Formation and Metastasis

History

ARTICLE ABSTRACT

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, Tgfbr2, was conditionally deleted in the mammary epithelium (Tgfbr2MGKO). Loss of Tgfbr2 in the mammary epithelium results in lobular-alveolar hyperplasia in the developing mammary gland and increased apoptosis. Tgfbr2MGKO mice were mated to the mouse mammary tumor virus-polyomavirus middle T antigen (PyVmT) transgenic mouse model of metastatic breast cancer. Loss of Tgfbr2 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.