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Tumorigenesis

Getting under the skin

Nature Reviews Cancer volume 3, page 153 (2003)Cite this article

The transcriptional regulator NF-κB regulates several signalling pathways, including those that are involved in cell proliferation and apoptosis. In many tumours, activated NF-κB promotes proliferation and inhibits apoptosis, but reports have shown that inhibition of NF-κB actually causes increased proliferation in the skin. In the 6 February issue of Nature, Maya Dajee et al. further explore the role of NF-κB in skin tumorigenesis.

The authors expressed activated oncogene HRAS either alone or with the NF-κB subunit p65 or a stable mutant of IκBα — which causes NF-κB to remain inactive in the cytoplasm — in primary human keratinocytes and grafted these cells onto immunodeficient mice. RAS expression stimulates growth in most cell systems, but in this model it inhibited growth in the skin. Co-expression of RAS and NF-κB subunits also inhibited proliferation. The co-expression of RAS and stabilized IκBα allowed the cell to overcome growth arrest induced by activated RAS, leading to the formation of large squamous-cell carcinomas (SCCs). Tumours from patients with SCC had NF-κB in the cytoplasm and a subset also had increased expression of IκBα and RAS, supporting the relevance of RAS and NF-κB activation in some spontaneous human SCCs.

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References

ORIGINAL RESEARCH PAPER

  1. Dajee, M. et al. NF-κB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature 421, 639–643 (2003)

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FURTHER READING

  1. Karin, M. et al. NF-κB in cancer: from innocent bystander to major culprit. Nature Rev. Cancer 2, 301–310 (2002)

    Article  CAS  Google Scholar 

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Authors
  1. Ezzie Hutchinson
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Hutchinson, E. Getting under the skin. Nat Rev Cancer 3, 153 (2003). https://doi.org/10.1038/nrc1034

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  • DOI: https://doi.org/10.1038/nrc1034

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