Conditional expression of the dominant-negative TGF-β receptor type II elicits lingual epithelial hyperplasia in transgenic mice.
BACKGROUND
The transforming growth factor-β (TGF-β) signaling pathway is generally believed to be a potent inhibitor of proliferation. However, many epithelia lacking the essential Tgfbr2 gene still maintain normal tissue homeostasis. Here, transgenic mice expressing rtTA from the human keratin 14 (K14) promoter were used to generate an inducible dominant-negative TGF-β receptor type II (Tgfbr2) mutant model, which allowed us to distinguish between the primary and secondary effects of TGF-β signaling disruption by Doxycycline treatment in K14+ epithelial stem cells.


RESULTS
We showed that in mice lacking TGF-β signaling in K14+ cells, invasive carcinomas developed on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface showed different pathological changes from the tip to the posterior of the tongue. In addition, acetylation levels of histone H4 and histone H3 rapidly increased, while pMAPK activity was enhanced and Jagged2 inactivated in lingual epithelia after disruption of TGF-β signaling.


CONCLUSIONS
Our results contribute to the understanding of TGF-β signaling in regulating homeostasis and carcinogenesis in lingual epithelia.
School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, People's Republic of China. lifengwest@gmail.com
Feng
F
Li
Mingliang
M
Zhou
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005799:Genes, Dominant / Q000502:physiology*; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000502:physiology; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology; D014059:Tongue / Q000378:metabolism / Q000473:pathology*; D014062:Tongue Neoplasms / Q000235:genetics / Q000473:pathology
D050505:Mutant Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II