Skip to main content

Advertisement

SpringerLink
Log in

Strong expression of a longevity-related protein, SIRT1, in Bowen’s disease

  • Short Communication
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead transcription factors, and overexpression of SIRT1 is reported to be essential for cell growth and survival in some kinds of cancer. To elucidate the role of SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in 20 cases each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen’s disease (BD), and actinic keratosis (AK) by immunohistochemical analysis. Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin cancers included in this study. In particular, strong expression was observed in all cases of BD. In addition, no obvious difference between AK and SCC was observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis. We suppose that SIRT1 could be one of the critical targets for future therapy with the aim of inhibiting cell proliferation and promoting apoptosis in non-melanoma skin cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Brasanac D, Boricic I, Todorovic V, Tomanovic N, Radojevic S (2005) Cyclin A and β-catenin expression in actinic keratosis, Bowen’s disease and invasive squamous cell carcinoma of the skin. Br J Dermatol 153:1166–1175

    Article  PubMed  CAS  Google Scholar 

  2. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng H-L, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–2015

    Article  PubMed  CAS  Google Scholar 

  3. Chen WY, Wang DH, Yen RWC, Luo J, Gu W, Baylin SB (2005) Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell 123:437–448

    Article  PubMed  CAS  Google Scholar 

  4. Ford J, Jiang M, Milner J (2005) Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival. Cancer Res 65:10457–10463

    Article  PubMed  CAS  Google Scholar 

  5. Heltweg B, Gatbonton T, Schuler AD, Posakony J, Li H, Goehle S, Kollipara R, DePinho RA, Gu Y, Simon JA, Bedalov A (2006) Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res 66:4368–4377

    Article  PubMed  CAS  Google Scholar 

  6. Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403:795–800

    Article  PubMed  CAS  Google Scholar 

  7. Kuzmichev A, Margueron R, Vaquero A, Preissner TS, Scher M, Kirmizis A, Ouyang X, Brockdorff N, Abate-Shen C, Farnham P, Reinberg D (2005) Composition and histone substrate of polycomb repressive group complexes change during cellular differentiation. PNAS 102:1859–1864

    Article  PubMed  CAS  Google Scholar 

  8. Lim CS (2006) SIRT1: tumor promoter or suppressor? Med Hypotheses 67:341–344

    Article  PubMed  CAS  Google Scholar 

  9. Longo VD, Kennedy BK (2006) Sirtuins in aging and age-related disease. Cell 126:257–268

    Article  PubMed  CAS  Google Scholar 

  10. Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116:551–563

    Article  PubMed  CAS  Google Scholar 

  11. Murao K, Kubo Y, Fukuhara K, Matsumoto K, Arase S (2005) Three cases of Bowen’s disease on the lower abdomen associated with high-risk types 16, 33, and 59 of human papillomavirus. J Am Acad Dermatol 52:723–724

    Article  PubMed  Google Scholar 

  12. Murao K, Kubo Y, Takiwaki H, Arase S, Matsumoto K (2005) Bowen’s disease on the sole: p16INK4a overexpression associated with human papillomavirus type 16. Br J Dermatol 152:170–173

    Article  PubMed  CAS  Google Scholar 

  13. Ota H, Tokunaga E, Chang K, Hikasa M, Iijima K, Eto M, Kozaki K, Akishita M, Ouchi Y, Kaneki M (2006) SIRT1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 25:176–185

    PubMed  CAS  Google Scholar 

  14. Salama ME, Mahmood MN, Qureshi HS, Ma C, Zarbo RJ, Ormsby AH (2003) Dermatopathology p16INK4a expression in actinic keratosis and Bowen’s disease. Br J Dermatol 149:1006–1012

    Article  PubMed  CAS  Google Scholar 

  15. Sherr CJ, McCormick F (2002) The RB and p53 pathways in cancer. Cancer Cell 2:103–112

    Article  PubMed  CAS  Google Scholar 

  16. Vaziri H, Dessain SK, Eaton EN, Imai S-I, Frye RA, Pandita TK, Guarente L, Weinberg RA (2001) hSIR2SIRT1 function as an NAD-dependent p53 deacetylase. Cell 107:149–159

    Article  PubMed  CAS  Google Scholar 

  17. Voelter-Mahlknecht S, Mahlknecht U (2006) Cloning, chromosomal characterization and maping of the NAD-dependent histone deacetylases gene sirtuin 1. Int J Mol Med 17:59–67

    PubMed  CAS  Google Scholar 

  18. Wang C, Chen L, Hou X, Li Z, Kabra N, Ma Y, Nemoto S, Finkel T, Gu W, Cress WD, Chen J (2006) Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nature Cell Biol 8:1025–1031

    Article  PubMed  CAS  Google Scholar 

  19. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. ENBO J 23:2369–2380

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Department of Dermatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    Yasutoshi Hida, Yoshiaki Kubo, Kazutoshi Murao & Seiji Arase

Authors
  1. Yasutoshi Hida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshiaki Kubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazutoshi Murao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seiji Arase
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshiaki Kubo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hida, Y., Kubo, Y., Murao, K. et al. Strong expression of a longevity-related protein, SIRT1, in Bowen’s disease. Arch Dermatol Res 299, 103–106 (2007). https://doi.org/10.1007/s00403-006-0725-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-006-0725-6

Keywords

Search

Navigation