Suppression of type I interferon signaling proteins is an early event in squamous skin carcinogenesis

John L. Clifford, Eugene Walch, Xiulan Yang, Xiaochun Xu, David S. Alberts, Gary L. Clayman, Adel K. El-Naggar, Reuben Lotan, Scott M. Lippman

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Purpose: IFN-based therapy has been shown to be active in the treatment of squamous cell carcinoma (SCC) of the skin, the most aggressive form of non-melanoma skin cancer. Based largely on this activity, we began programmatically examining the expression of IFN-stimulated gene factor 3 (ISGF-3) proteins (signal transducers and activators of transcription 1α/β, signal transducers and activators of transcription 2, and p48), which are important mediators of IFN-α signaling, in skin premalignancy and SCC. Our previous preliminary studies suggested suppression of some or all of the ISGF-3 proteins in skin SCC. Experimental Design: To determine the timing of the suppression of IFN-α signaling proteins in squamous skin carcinogenesis, we have now compared ISGF-3 expression by immunohistochemical staining in biopsies of actinic keratosis, a form of skin premalignancy, and matched normal skin. Results: We observed a significant decrease in expression of one or more ISGF-3 proteins in 76% of patients with actinic keratosis (19 of 25 patients). In addition, we found a suppression of one or more ISGF-3 proteins in 67% of skin SCC patients tested (12 of 18 patients), confirming our previous observations. Conclusions: These data have led to the hypothesis that the suppressed expression of ISGF-3 proteins and consequent reduction in responsiveness to endogenous IFN likely are an early event in skin carcinogenesis.

Original languageEnglish (US)
Pages (from-to)2067-2072
Number of pages6
JournalClinical Cancer Research
Issue number7
StatePublished - 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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