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DEK proto-oncogene expression interferes with the normal epithelial differentiation program.

Publication ,  Journal Article
Wise-Draper, TM; Morreale, RJ; Morris, TA; Mintz-Cole, RA; Hoskins, EE; Balsitis, SJ; Husseinzadeh, N; Witte, DP; Wikenheiser-Brokamp, KA ...
Published in: Am J Pathol
January 2009

Overexpression of the DEK gene is associated with multiple human cancers, but its specific roles as a putative oncogene are not well defined. DEK transcription was previously shown to be induced by the high-risk human papillomavirus (HPV) E7 oncogene via E2F and Rb pathways. Transient DEK overexpression was able to inhibit both senescence and apoptosis in cultured cells. In at least the latter case, this mechanism involved the destabilization of p53 and the decreased expression of p53 target genes. We show here that DEK overexpression disrupts the normal differentiation program in a manner that is independent of either p53 or cell death. DEK expression was distinctly repressed upon the differentiation of cultured primary human keratinocytes, and stable DEK overexpression caused epidermal thickening in an organotypic raft model system. The observed hyperplasia involved a delay in keratinocyte differentiation toward a more undifferentiated state, and expansion of the basal cell compartment was due to increased proliferation, but not apoptosis. These phenotypes were accompanied by elevated p63 expression in the absence of p53 destabilization. In further support of bona fide oncogenic DEK activities, we report here up-regulated DEK protein levels in both human papilloma virus-positive hyperplastic murine skin and a subset of human squamous cell carcinomas. We suggest that DEK up-regulation may contribute to carcinoma development at least in part through increased proliferation and retardation of differentiation.

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Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

January 2009

Volume

174

Issue

1

Start / End Page

71 / 81

Location

United States

Related Subject Headings

  • Up-Regulation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proto-Oncogene Mas
  • Poly-ADP-Ribose Binding Proteins
  • Pathology
  • Papillomavirus E7 Proteins
  • Oncogene Proteins
  • Mice, Transgenic
  • Mice
  • Membrane Proteins
 

Citation

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ICMJE
MLA
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Wise-Draper, T. M., Morreale, R. J., Morris, T. A., Mintz-Cole, R. A., Hoskins, E. E., Balsitis, S. J., … Wells, S. I. (2009). DEK proto-oncogene expression interferes with the normal epithelial differentiation program. Am J Pathol, 174(1), 71–81. https://doi.org/10.2353/ajpath.2009.080330
Wise-Draper, Trisha M., Richard J. Morreale, Teresa A. Morris, Rachael A. Mintz-Cole, Elizabeth E. Hoskins, Scott J. Balsitis, Nader Husseinzadeh, et al. “DEK proto-oncogene expression interferes with the normal epithelial differentiation program.Am J Pathol 174, no. 1 (January 2009): 71–81. https://doi.org/10.2353/ajpath.2009.080330.
Wise-Draper TM, Morreale RJ, Morris TA, Mintz-Cole RA, Hoskins EE, Balsitis SJ, et al. DEK proto-oncogene expression interferes with the normal epithelial differentiation program. Am J Pathol. 2009 Jan;174(1):71–81.
Wise-Draper, Trisha M., et al. “DEK proto-oncogene expression interferes with the normal epithelial differentiation program.Am J Pathol, vol. 174, no. 1, Jan. 2009, pp. 71–81. Pubmed, doi:10.2353/ajpath.2009.080330.
Wise-Draper TM, Morreale RJ, Morris TA, Mintz-Cole RA, Hoskins EE, Balsitis SJ, Husseinzadeh N, Witte DP, Wikenheiser-Brokamp KA, Lambert PF, Wells SI. DEK proto-oncogene expression interferes with the normal epithelial differentiation program. Am J Pathol. 2009 Jan;174(1):71–81.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

January 2009

Volume

174

Issue

1

Start / End Page

71 / 81

Location

United States

Related Subject Headings

  • Up-Regulation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proto-Oncogene Mas
  • Poly-ADP-Ribose Binding Proteins
  • Pathology
  • Papillomavirus E7 Proteins
  • Oncogene Proteins
  • Mice, Transgenic
  • Mice
  • Membrane Proteins