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SHP-1 promoter 2 methylation in normal epithelial tissues and demethylation in psoriasis

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Abstract

SHP-1 promoter hypermethylation has been studied in hematopoietic cells and observed only in various types of lymphoma and leukemia. This study reports a contrasting situation in normal epithelial tissues and an association with skin pathogenesis, particularly in psoriasis. We investigated several cell lines, five of them were epithelial and six were hematopoietic, white blood cells from normal, healthy donors, and normal microdissected epithelium of kidney, liver, breast, cervix, lung, prostate, bladder, and skin. Interestingly, promoter 2 hypermethylation was apparent in all epithelial cell lines and tissues. However, distinctive degrees of demethylation were noted in some skin samples. The methylation patterns of each cell line corresponded to their mRNA isoforms, in that isoforms I and II could not be detected with either promoter 1 or 2 hypermethylation, respectively. We further explored whether an enhanced degree of demethylation could be observed in various dermatopathology lesions. While the promoter 2 methylation levels of squamous cell cancers, eczemas, and normal skins were not different, a significant degree of demethylation can be observed in psoriasis (p<0.005). In addition, psoriasis displays a higher level of SHP-1 isoform II than normal skin (p<0.05). In conclusion, this study discovered an unprecedented role of SHP-1 methylation in tissue-specific expression and its alteration in a nonmalignant human disease besides the transcription inhibition in leukemia and lymphoma. Furthermore, the promoter demethylation may play an important role in skin pathogenesis by enhancing SHP-1 isoform II transcription in psoriatic skin lesions.

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Abbreviations

SCC:

Squamous cell carcinoma

COBRA:

combined bisulfite restriction analysis

MSP:

methylation-specific PCR

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Acknowledgements

This work was supported in part by grants from the Royal Golden Jubilee Ph.D. grant, the Thailand Research Funds, Molecular Biology and Genetics of Cancer Development Research Unit, Chulalongkorn University, and National Center for Genetic Engineering and Biotechnology, Thailand. For cell lines, we thank Professor Hedeoki Ogawa for kindly providing HaCaT, Dr. Chintana Chirathaworn for U937 and Molt4, Dr. Virote Sriuranpong for Hela and SW480, Dr. Watchara Kasinrerk for Daudi, Jurkat, and K562, and Dr. Pokrath Hansasura for both BLCLs. We also would like to express our gratitude to the Department of Pathology, Dermatology Unit, Department of Medicine, and our professor, Dr. Nopadon Noppakun, for paraffin tissues and clinical information. Finally, we would like to thank Ms. Petra Hirsch for critically reviewing the manuscript.

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Authors and Affiliations

  1. Inter-Department of Biomedical Sciences, Graduate School, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Kriangsak Ruchusatsawat

  2. Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Jongkonnee Wongpiyabovorn & Nattiya Hirankarn

  3. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Shanop Shuangshoti

  4. Department of Anatomy, Molecular Biology and Genetics of Cancer Development Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Apiwat Mutirangura

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  1. Kriangsak Ruchusatsawat
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  2. Jongkonnee Wongpiyabovorn
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  3. Shanop Shuangshoti
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  4. Nattiya Hirankarn
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  5. Apiwat Mutirangura
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Correspondence to Apiwat Mutirangura.

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Ruchusatsawat, K., Wongpiyabovorn, J., Shuangshoti, S. et al. SHP-1 promoter 2 methylation in normal epithelial tissues and demethylation in psoriasis. J Mol Med 84, 175–182 (2006). https://doi.org/10.1007/s00109-005-0020-6

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  • DOI: https://doi.org/10.1007/s00109-005-0020-6

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