Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Irina V. Budunova, Paloma Perez, Valerie R. Vaden, Vladimir S. Spiegelman, Thomas J. Slaga, Jose L. Jorcano

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

To elucidate the possible role of NF-κB in mouse skin carcinogenesis we studied the expression of p50 (NF-κB1), p52 (NF-κB2), p65 (RelA) and IκB-α inhibitor as well as κB-binding activity in adult SENCAR mouse skin, skin papillomas, and squamous cell carcinomas (SCC) generated by a two-stage carcinogenesis protocol. We found that in normal epidermis all of the above proteins were mostly expressed in the cytoplasm of basal cells. Western blot analysis revealed a dramatic increase of p50 and p52 expression in mouse skin tumors starting from the middle stage of promotion. We also found that the level of IκB-α protein in many late papillomas and SCC was lower than in normal epidermis. Results of EMSA showed an increase in κB-binding activity in mouse skin tumors and suggested that p50 is the major component of constitutive κB-binding complexes in normal epidermis and in tumors. It has been shown that nuclear IκB protein Bcl-3 is able to increase p50/p50 homodimer binding to the different IκB sites in mouse thymocytes. Our finding on Bcl-3 overexpression in late papillomas and SCC could explain the selective increase of p50-related κB-binding in mouse skin tumors. Thus, our results strongly suggest the important role of p50 in skin carcinogenesis.

Original languageEnglish (US)
Pages (from-to)7423-7431
Number of pages9
JournalOncogene
Volume18
Issue number52
DOIs
StatePublished - Dec 9 1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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