Effect of conditional knockout of the type II TGF-beta receptor gene in mammary epithelia on mammary gland development and polyomavirus middle T antigen induced tumor formation and metastasis.

Forrester E, Chytil A, Bierie B, Aakre M, Gorska AE, Sharif-Afshar AR, Muller WJ, Moses HL
Cancer Res. 2005 65 (6): 2296-302

PMID: 15781643 · DOI:10.1158/0008-5472.CAN-04-3272

Transforming growth factor-beta (TGF-beta) isoforms are growth factors that function physiologically to regulate development, cellular proliferation, and immune responses. The role of TGF-beta signaling in mammary tumorigenesis is complex, as TGF-beta has been reported to function as both a tumor suppressor and tumor promoter. To elucidate the role of TGF-beta signaling in mammary gland development, tumorigenesis, and metastasis, the gene encoding type II TGF-beta 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-beta signaling in mammary gland tumorigenesis and show that pulmonary metastases can occur and are even enhanced in the absence of TGF-beta signaling in the carcinoma cells.

MeSH Terms (20)

Animals Antigens, Polyomavirus Transforming Cell Growth Processes Cell Transformation, Neoplastic Epithelial Cells Female Hyperplasia Lung Neoplasms Male Mammary Glands, Animal Mammary Neoplasms, Experimental Mammary Tumor Virus, Mouse Mice Mice, Inbred C57BL Mice, Knockout Protein-Serine-Threonine Kinases Pulmonary Alveoli Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta Transgenes

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