NF-κB blockade and oncogenic Ras trigger invasive human epidermal neoplasia

Maya Dajee, Mirella Lazarov, Jennifer Y. Zhang, Ti Cai, Cheryl L. Green, Alan J. Russell, M. Peter Marinkovich, Shiying Tao, Qun Lin, Yoshiaki Kubo and Paul A. Khavari ()
Additional contact information
Maya Dajee: Stanford University School of Medicine
Mirella Lazarov: Stanford University School of Medicine
Jennifer Y. Zhang: Stanford University School of Medicine
Ti Cai: Stanford University School of Medicine
Cheryl L. Green: Stanford University School of Medicine
Alan J. Russell: Stanford University School of Medicine
M. Peter Marinkovich: Stanford University School of Medicine
Shiying Tao: Stanford University School of Medicine
Qun Lin: Stanford University School of Medicine
Yoshiaki Kubo: Stanford University School of Medicine
Paul A. Khavari: Stanford University School of Medicine

Nature, 2003, vol. 421, issue 6923, 639-643

Abstract: Abstract The nuclear factor NF-κB and oncogenic Ras can alter proliferation in epidermis, the most common site of human cancer1,2. These proteins are implicated in epidermal squamous cell carcinoma in mice3,4,5, however, the potential effects of altering their function are uncertain. Whereas inhibition of NF-κB enhances apoptosis in certain tumours6, blockade of NF-κB predisposes murine skin to squamous cell carcinoma5,7. Because therapeutics inhibiting Ras and NF-κB pathways are being developed to treat human cancer8,9, it is essential to assess the effects of altering these regulators. The medical relevance of murine studies is limited, however, by differences between mouse and human skin, and by the greater ease of transforming murine cells. Here we show that in normal human epidermal cells both NF-κB and oncogenic Ras trigger cell-cycle arrest. Growth arrest triggered by oncogenic Ras can be bypassed by IκBα-mediated blockade of NF-κB, generating malignant human epidermal tissue resembling squamous cell carcinoma. Human cell tumorigenesis is dependent on laminin 5 and α6β4 integrin. Thus, IκBα circumvents restraints on growth promotion induced by oncogenic Ras and can act with Ras to induce invasive human tissue neoplasia.

Date: 2003
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature01283 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:421:y:2003:i:6923:d:10.1038_nature01283

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01283

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().