Abstract
Tongue epithelium continuously turns over in adults. Our previous study showed that epidermal growth factor and fibroblast growth factor-2 stimulated proliferation of KT-1 cells derived from tongue epithelium, suggesting that these signals serve as positive regulators for tongue epithelial proliferation. To investigate a negative regulation of tongue epithelial cell proliferation, we studied effects of transforming growth factor-β (TGF-β) on KT-1 cells. Proliferation assays showed that TGF-β inhibited proliferation of KT-1 cells in a dose dependent manner. Cell-cycle analysis showed that TGF-β induced G0/G1 cell cycle arrest in KT-1 cells. We also examined expressions of Ink4 and Cip/Kip family mRNA by quantitative reverse transcription-polymerase chain reaction. We found that TGF-β induced p15Ink4b and p21Cip1 mRNA expressions. These results strongly suggest that G0/G1 cell cycle arrest is associated with increased p15Ink4b and p21Cip1 expressions. Moreover, p21Cip1 mRNA was localized in suprabasal cells of tongue epithelium, suggesting that p21Cip1 play a role in cell-cycle exit along with tongue epithelial differentiation. Taken together, our results suggest that TGF-β signaling serves as negative regulator of tongue epithelial cell proliferation, and may control tongue epithelial cell differentiation through modulating expression of p21Cip1.
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Acknowledgments
The authors express their gratitude to Dr. Yuko Kusakabe, Dr. Takayuki Kawai, Ms. Yumiko Ito, Mr. Takeshi Ebihara, Ms. Mariko Kobayashi, Ms. Hiromi Kato, and Ms. Yuriko Hino for their help in the experiments and to the members of the Kamakura-laboratory for helpful discussions. We also thank Dr. Shigeru Yasumoto for numerous and valuable discussions. This work was financially supported by the National Food Research Institute and Japan Science and Technology Agency.
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Nakamura, Si., Kamakura, T. & Ookura, T. Tongue epithelial KT-1 cell-cycle arrest by TGF-β associated with induction of p21Cip1 and p15Ink4b . Cytotechnology 61, 109–116 (2009). https://doi.org/10.1007/s10616-010-9251-7
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DOI: https://doi.org/10.1007/s10616-010-9251-7