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

Oncogene volume 18, pages 7423–7431 (1999)Cite this article

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 κB 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.

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Abbreviations

DMBA:

7,12-dimethylbenz(a)anthracene

SCC:

squamous cell carcinoma

TPA:

12-O-tetradecanoyl-phorbol-13-acetate

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Acknowledgements

We gratefully acknowledge Drs Rolf-Peter Ryseck and Rodrigo Bravo (Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA) for their gift of p50 polyclonal antibody. We thank Dr Fernando Larcher (Department of Cell and Molecular Biology, CIEMAT, Madrid, Spain) for valuable comments. Grant support: National Cancer Institute grant CA79065-02.

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Authors and Affiliations

  1. AMC Cancer Research Center, 1600 Pierce Street, Denver, 80214, Colorado, CO, USA

    Irina V Budunova, Valerie R Vaden, Vladimir S Spiegelman & Thomas J Slaga

  2. Department of Cell and Molecular Biology, CIEMAT, Av, Complutense 22, 28040, Madrid, Spain

    Paloma Perez & Jose L Jorcano

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  1. Irina V Budunova
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  2. Paloma Perez
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Budunova, I., Perez, P., Vaden, V. et al. Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis. Oncogene 18, 7423–7431 (1999). https://doi.org/10.1038/sj.onc.1203104

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