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Updated: Sep 25, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary
Peter M Siegel1, Weiping Shu, Robert D Cardiff
1Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Abstract:
The influence of transforming growth factor beta (TGF-beta) signaling on Neu-induced mammary tumorigenesis and metastasis was examined with transgenic mouse models. We generated mice expressing an activated TGF-beta type I receptor or dominant negative TGF-beta type II receptor under control of the mouse mammary tumor virus promoter. When crossed with mice expressing activated forms of the Neu receptor tyrosine kinase that selectively couple to the Grb2 or Shc signaling pathways the activated type I receptor increased the latency of mammary tumor formation but also enhanced the frequency of extravascular lung metastasis. Conversely, expression of the dominant negative type II receptor decreased the latency of Neu-induced mammary tumor formation while significantly reducing the incidence of extravascular lung metastases. These observations argue that TGF-beta can promote the formation of lung metastases while impairing Neu-induced tumor growth and suggest that extravasation of breast cancer cells from pulmonary vessels is a point of action of TGF-beta in the metastatic process.
Insights
Transforming growth factor beta (TGF-beta) signaling impacts Neu-induced breast cancer. Activated TGF-beta I receptor delayed tumor growth but increased lung metastasis, while dominant-negative TGF-beta II receptor did the opposite.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Transforming growth factor beta (TGF-beta) signaling is crucial in cancer.
- Neu receptor tyrosine kinase activation drives mammary tumorigenesis.
- The interplay between TGF-beta and Neu signaling in metastasis is not fully understood.
Purpose of the Study:
- To investigate the role of TGF-beta signaling in Neu-induced mammary tumorigenesis and metastasis.
- To elucidate how TGF-beta receptor activity influences tumor growth and metastatic spread.
Main Methods:
- Generated transgenic mouse models expressing activated or dominant-negative TGF-beta receptors.
- Crossed these models with mice expressing activated Neu receptor tyrosine kinase.
- Analyzed mammary tumor formation latency and lung metastasis frequency.
Main Results:
- Activated TGF-beta type I receptor increased mammary tumor latency but enhanced lung metastasis.
- Dominant-negative TGF-beta type II receptor decreased tumor latency and lung metastasis.
- TGF-beta signaling appears to promote lung metastasis while inhibiting Neu-induced tumor growth.
Conclusions:
- TGF-beta signaling has a dual role in Neu-induced mammary cancer.
- TGF-beta promotes lung metastasis, potentially by affecting cancer cell extravasation.
- Targeting TGF-beta pathways could offer therapeutic strategies for breast cancer metastasis.
