Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

PUMA expression is significantly reduced in human cutaneous melanomas

Abstract

Cutaneous malignant melanoma is an aggressive form of skin cancer, characterized by strong chemoresistance and poor patient prognosis. The molecular mechanisms underlying its resistance to chemotherapy remain unclear but are speculated to involve the dysregulation of apoptotic pathways. In this study, we sought to determine whether PUMA (p53 upregulated modulator of apoptosis) contributes to human melanoma formation, tumor progression, and survival. We used tissue microarray and immunohistochemistry to examine PUMA expression in 107 primary melanomas, 51 metastatic melanomas, and 64 dysplastic nevi. Here we report that PUMA expression is significantly weaker in primary melanomas compared to dysplastic nevi (P<0.0001), and is further reduced in metastatic melanomas compared to primary tumors (P=0.001). We show that weak PUMA expression in melanoma correlates with poorer overall and disease-specific 5-year survival (P<0.005 and P<0.001, respectively) of melanoma patients and that PUMA expression in tumor tissue is an independent predictor of both overall and disease-specific 5-year survival (P=0.05). Additionally, we show that exogenous PUMA expression in human melanoma cell lines (both wild type and mutant p53) results in significant apoptotic cell death. Our results suggest that PUMA expression may be an important prognostic marker for human melanoma and that adenoviral delivery of PUMA sensitizes melanoma cells to apoptosis.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton Jr A, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA and Thompson JF . (2001). J. Clin. Oncol., 19, 3635–3648.

  • Bowen AR, Hanks AN, Allen SM, Alexander A, Diedrich MJ and Grossman D . (2003). J. Invest. Dermatol., 120, 48–55.

  • Chin L, Merlino G and DePinho RA . (1998). Genes Dev., 12, 3467–3481.

  • Fisher DE . (1994). Cell, 78, 539–542.

  • Glinsky GV, Glinsky VV, Ivanova AB and Hueser CJ . (1997). Cancer Lett., 115, 185–193.

  • Grossman D and Altieri DC . (2001). Cancer Metast Rev., 20, 3–11.

  • Grossman D, McNiff JM, Li F and Altieri DC . (1999). J. Invest. Dermatol., 113, 1076–1081.

  • Han J, Flemington C, Houghton AB, Gu Z, Zambetti GP, Lutz RJ, Zhu L and Chittenden T . (2001). Proc. Natl. Acad. Sci. USA, 98, 11318–11323.

  • Houghton AN and Polsky D . (2002). Cancer Cell, 2, 275–278.

  • Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE and Tschopp J . (1997). Nature, 388, 190–195.

  • Jemal A, Devesa SS, Hartge P and Tucker MA . (2001). J. Natl. Cancer Inst., 93, 678–683.

  • Jemal A, Thomas A, Murray T and Thun MJ . (2002). CA Cancer J. Clin., 52, 23–47.

  • Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ and Thun MJ . (2004). CA Cancer J. Clin., 54, 8–29.

  • Nakano K and Vousden KH . (2001). Mol. Cell, 7, 683–694.

  • Serrone L and Hersey P . (1999). Melanoma Res., 9, 51–58.

  • Serrone L, Zeuli M, Sega FM and Cognetti F . (2000). J. Exp. Clin. Cancer Res., 19, 21–34.

  • Soengas MS, Capodieci P, Polsky D, Mora J, Esteller M, Opitz-Araya X, McCombie R, Herman JG, Gerald WL, Lazebnik YA, Cordon-Cardo C and Lowe SW . (2001). Nature, 409, 207–211.

  • Soengas MS and Lowe SW . (2003). Oncogene, 22, 3138–3151.

  • Staunton MJ and Gaffney EF . (1995). Am. J. Clin. Pathol., 103, 300–307.

  • Yu J, Wang Z, Kinzler KW, Vogelstein B and Zhang L . (2003). Proc. Natl. Acad. Sci. USA, 100, 1931–1936.

  • Yu J, Zhang L, Hwang PM, Kinzler KW and Vogelstein B . (2001). Mol. Cell, 7, 673–682.

Download references

Acknowledgements

We thank Nhu Le for his assistance with statistical analyses, David Huntsman and Nikita Makretsov for help in tissue microarray construction, and Andrew Coldman for collecting patient survival data. This work was supported by grants from the National Cancer Institute of Canada to GL. AK is supported by the Michael Smith Foundation for Health Research and by the Natural Sciences and Engineering Research Council of Canada. GL is a recipient of the Research Scientist Award from the National Cancer Institute of Canada supported with funds provided by the Canadian Cancer Society.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gang Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karst, A., Dai, D., Martinka, M. et al. PUMA expression is significantly reduced in human cutaneous melanomas. Oncogene 24, 1111–1116 (2005). https://doi.org/10.1038/sj.onc.1208374

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208374

Keywords

This article is cited by

Search

Quick links