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Growth inhibition induced by transforming growth factor-β1 in human oral squamous cell carcinoma

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Abstract

Oral squamous cell carcinoma (OSCC) is a world-wide health problem and its incidence accounts for 1.9–3.5% of all malignant tumors. Transforming growth factor beta/Smads (TGF-β/Smads) signaling pathway plays an important role in oncogenesis, but its function and molecular mechanisms in OSCC remain unclear. Expression of transforming growth factor-β receptor type II (TβRII) and Smad4 was studied by immunohistochemistry in 108 OSCC patients and 10 normal controls. Function and molecular mechanisms of TGF-β/Smads signaling pathway was then investigated in two human tongue squamous carcinoma cell lines with high and low metastasis (Tb and Tca8113) by RT-PCR, Western Blot, immunofluorescence, cell growth curve and flow cytometry (FCM), respectively. TβRII and Smad4 were significantly down-regulated in tumor tissues (with or without lymph node metastasis) compared to normal oral epithelium tissues (P < 0.05). TGF-β1 induced arrest of the cell cycle rather than cell death in Tca8113 and Tb cells, and this influence was mediated by the increasing the expression and changing the location of its downstream components of TGF-β1/Smads signaling pathway. TGF-β1 rapidly increased the expression of p15 and p21 in both Tca8113 and Tb cells. TGF-β1 did not increase p27 expression in Tca8113 cells, but p27 expression was increased in Tb cells. These indicated that TGF-β1 induced G1 arrest of cell cycle through a different regulating pathway in Tb cells compared with Tca8113 cells. Thus, we conclude that TGF-β/Smads signaling pathway play a important role on cell growth and metastasis potential in OSCC.

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Acknowledgements

We thank all sample donors for taking part in this study. This work is supported by the National 973(2001CD510300) projects and 863(2002BA711A08) projects and Heilongjiang province natural science fund (D-0326) projects of China; Heilongjiang province natural science fund (D2007-01); post-doctoral grant of HeiLongJiang Province (LRB05-279).

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Authors and Affiliations

  1. The Second Affiliated Hospital, Harbin Medical University, Harbin, 150081, China

    Xiumei Wang

  2. Laboratory of Medical Genetics, Harbin Medical University, Harbin, 150081, China

    Xiumei Wang, Wenjing Sun, Jing Bai, Linlin Ma, Yang Yu, Zhongcheng Shi & Songbin Fu

  3. Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, China

    Jing Bai & Songbin Fu

  4. The Third Affiliated Hospital, Harbin Medical University, Harbin, 150081, China

    Jingshu Geng

  5. The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China

    Jiping Qi

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  1. Xiumei Wang
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  2. Wenjing Sun
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  9. Songbin Fu
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Corresponding author

Correspondence to Songbin Fu.

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Xiumei Wang, Wenjing Sun, and Jing Bai contributed equally to this paper.

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Wang, X., Sun, W., Bai, J. et al. Growth inhibition induced by transforming growth factor-β1 in human oral squamous cell carcinoma. Mol Biol Rep 36, 861–869 (2009). https://doi.org/10.1007/s11033-008-9256-x

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  • DOI: https://doi.org/10.1007/s11033-008-9256-x

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