Abstract
Transforming growth factor-β (TGF-β) signals through serine/threonine-kinase receptors to activate several intracellular signaling pathways, including the “canonical” Smad signaling pathway. TGF-β has tumor-suppressive functions through its capacity to induce growth arrest and apoptosis. Escape from the anti-proliferative effects of TGF-β is a hallmark of almost all tumors of epithelial origin. This chapter first depicts the genetic alterations ablating the TGF-β tumor-suppressive functions in human tumors. Then, the chapter presents the genetically engineered mouse models that have been developed by introducing genetic alterations found in humans. These mouse models demonstrated the tumor-suppressive role of TGF-β in vivo shedding light on its intricate relationship with the tumor microenvironment. In all, the presented mouse models of cancer with an impaired TGF-β signaling pathway provide an integrated view of the complex tumor-suppressive role of TGF-β and represent valuable tools for preclinical studies.
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Abbreviations
- ALK5:
-
Activin receptor-like kinase 5
- AOM:
-
Azoxymethane
- APC:
-
Adenomatous polyposis coli
- BMP:
-
Bone morphogenetic protein
- BMPR1A:
-
Bone morphogenetic protein receptor, type IA
- CTGF:
-
Connective tissue growth factor
- DEN:
-
Diethylnitrosamine
- DMBA:
-
7,12-Dimethylbenz(α)anthracene
- DPC4:
-
Deleted in pancreatic carcinoma 4
- ELF:
-
Embryonic liver fodrin
- EMT:
-
Epithelial-to-mesenchymal transition
- FAP:
-
Familial adenomatous polyposis
- HoCC:
-
Homotypic cell cannibalism
- IPMN:
-
Intraductal papillary mucinous neoplasms
- KSSTT:
-
Pdx1-Cre; KRASG12D; Smad4-KOL/L; TIF1γ-KOL/L
- LOH:
-
Loss of heterozygosity
- LRP:
-
Low-density lipoprotein receptor-related protein
- LSL:
-
Lox-stop-lox
- MAPK:
-
Mitogen-activated protein kinase
- MCN:
-
Mucinous cystic neoplasms
- Min:
-
Multiple intestinal neoplasia
- MMP:
-
Matrix metalloproteinase
- MMTV:
-
Mouse mammary tumor virus
- MSI:
-
Microsatellite instability
- PanIN:
-
Pancreatic intraepithelial neoplasms
- PDAC:
-
Pancreatic ductal adenocarcinoma
- PDGF:
-
Platelet-derived growth factor
- PyVmT:
-
Polyoma virus middle T antigen
- SCC:
-
Squamous cell carcinoma
- TGF-β:
-
Transforming growth factor β
- TGF-α:
-
Transforming growth factor α
- TIF1:
-
Transcriptional intermediary factor 1
- TPA:
-
12-O-tetradecanoylphorbol-13-acetate
- TβRI:
-
TGF-β type I receptor
- TβRII:
-
TGF-β type II receptor
- WAP:
-
Whey acidic protein
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Valcourt, U., Vincent, D.F., Bartholin, L. (2013). TGF-β as Tumor Suppressor: Lessons from Mouse Models. In: Moustakas, A., Miyazawa, K. (eds) TGF-β in Human Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54409-8_6
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