Malignant transformation of immortalized HaCaT keratinocytes through deregulated nuclear factor κB signaling

Qing Ren, Csaba Kari, Marlene R D Quadros, Randy M Burd, Peter McCue, Adam P. Dicker, Ulrich Rodeck

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Previous studies addressing functional aspects of nuclear factor κB (NF-κB) activation in normal and transformed keratinocytes revealed complex and seemingly contradictory roles of this transcription factor in this cell type. In normal skin, NF-κB signaling seems to inhibit squamous cell carcinoma development whereas, in squamous cell carcinoma themselves, deregulated NF-κB expression and/or signaling is frequently observed. To further investigate this paradox, we focused on NF-κB activation as it relates to the transformed phenotype of immortalized but nontumorigenic human keratinocytes (HaCaT cells). We observed that NF-κB activity contributed to survival and growth of cultured HaCaT keratinocytes as shown by use of pharmacologic NF-κB inhibitors, BNA interference, and inducible overexpression of a dominant interfering IκB construct. NF-κB activation was largely provided through interaction with extracellular matrix components because preventing cell attachment by forced suspension culture markedly reduced NFκB signaling associated with cell death (anoikis); conversely, anoikis was partially reversed by NF-κB activation induced either by tumor necrosis factor-α treatment or by overexpressing the NF-κB p65 subunit in HaCaT cells. Furthermore, overexpression of NF-κBp65 in HaCaT cells induced colony formation in soft agar and tumorigenicity in nude mice. In summary, as opposed to normal keratinocytes, immortalized HaCaT keratinocytes provide a cellular context in which deregulated NF-κB signaling supports multiple malignant traits in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)5209-5215
Number of pages7
JournalCancer Research
Volume66
Issue number10
DOIs
StatePublished - May 15 2006
Externally publishedYes

Fingerprint

Keratinocytes
Anoikis
Squamous Cell Carcinoma
Nude Mice
Agar
Extracellular Matrix
Suspensions
Cell Death
Transcription Factors
Tumor Necrosis Factor-alpha
Phenotype
Skin
Survival
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Malignant transformation of immortalized HaCaT keratinocytes through deregulated nuclear factor κB signaling. / Ren, Qing; Kari, Csaba; Quadros, Marlene R D; Burd, Randy M; McCue, Peter; Dicker, Adam P.; Rodeck, Ulrich.

In: Cancer Research, Vol. 66, No. 10, 15.05.2006, p. 5209-5215.

Research output: Contribution to journalArticle

Ren, Qing ; Kari, Csaba ; Quadros, Marlene R D ; Burd, Randy M ; McCue, Peter ; Dicker, Adam P. ; Rodeck, Ulrich. / Malignant transformation of immortalized HaCaT keratinocytes through deregulated nuclear factor κB signaling. In: Cancer Research. 2006 ; Vol. 66, No. 10. pp. 5209-5215.
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