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Aberrant expression of p-Smad3 in oral carcinogenesis

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Abstract

Objective

Smads are the keys of transforming growth factor β (TGFβ) signaling cascade and play a crucial role in many cancers. Once TGFβ receptors are activated, Smad2 and Smad3 are phosphorylated and form complexes with Smad4. These complexes translocate from the cytoplasm to the nucleus where they regulate the target genes. The subcellular localization of phosphorylated Smad3 (p-Smad3) in oral carcinogenesis has never been reported. This study investigated the subcellular distribution of p-Smad3 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) with and without dysplasia.

Materials and methods

Expression of p-Smad3 was immunohistochemically examined in 150 samples including OSCC, OL with and without dysplasia, and normal mucosa (NM). Cytoplasmic and nuclear positive cells were counted separately. The results were present as the frequency of positive cases.

Results

Cytoplasmic and/or nuclear staining for p-Smad3 was detected. The frequency of cytoplasmic expression in OL with dysplasia was significantly higher than that in NM. The numbers of cytoplasmic expression and cytoplasmic plus nuclear expression in OSCC were significantly higher than those in NM and OL with and without dysplasia.

Conclusions

The overexpression of cytoplasmic p-Smad3 in OL with dysplasia and in OSCC suggests that p-Smad3 is in the nonfunctional state. Thus, the growth inhibitory effect of p-Smad3 is diminished during oral carcinogenesis. The cytoplasmic plus nuclear staining of p-Smad3 was aberrant in OSCC.

Clinical relevance

The cytoplasmic staining of p-Smad3 may serve as a marker for oral premalignant lesions whereas the cytoplasmic plus nuclear staining of p-Smad3 may serve as a marker for OSCC.

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Acknowledgments

This study was supported by the Thailand Research Fund. The authors would like to thank Mrs. Unruen Meesakul for her technical assistance and staff of the Department of the Oral Medicine and the Department of Oral and Maxillofacial Pathology for their assistance in this study.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Yothi Street, Bangkok, 10400, Thailand

    Sopee Poomsawat & Jirapa Punyasingh

  2. Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Paisarn Vejchapipat

Authors
  1. Sopee Poomsawat
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  2. Jirapa Punyasingh
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  3. Paisarn Vejchapipat
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Correspondence to Sopee Poomsawat.

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Poomsawat, S., Punyasingh, J. & Vejchapipat, P. Aberrant expression of p-Smad3 in oral carcinogenesis. Clin Oral Invest 19, 613–618 (2015). https://doi.org/10.1007/s00784-014-1281-7

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  • DOI: https://doi.org/10.1007/s00784-014-1281-7

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