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

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

Research output: Contribution to journalArticle

44 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Malignant transformation of immortalized HaCaT keratinocytes through deregulated nuclear factor κB signaling'. Together they form a unique fingerprint.

  • Cite this