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Updated: Sep 30, 2026

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Suppression of type I interferon signaling proteins is an early event in squamous skin carcinogenesis
John L Clifford1, Eugene Walch, Xiulan Yang
1Departments of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jclifford@mdanderson.org
Purpose:
IFN-based therapy has been shown to be active in the treatmentof 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 1alpha/beta, signal transducers and activators of transcription 2, and p48), which are important mediators of IFN-alpha 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-alpha 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.
Insights
Suppressed expression of IFN-stimulated gene factor 3 (ISGF-3) proteins, key to IFN-alpha signaling, is an early event in skin carcinogenesis. This occurs in both actinic keratosis and squamous cell carcinoma (SCC).
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Interferon (IFN)-based therapy shows efficacy in treating squamous cell carcinoma (SCC) of the skin.
- IFN-stimulated gene factor 3 (ISGF-3) proteins are critical mediators of IFN-alpha signaling.
- Previous studies indicated potential suppression of ISGF-3 proteins in skin SCC.
Purpose of the Study:
- To investigate the timing of ISGF-3 protein suppression during squamous skin carcinogenesis.
- To compare ISGF-3 expression in premalignant actinic keratosis and normal skin.
Main Methods:
- Immunohistochemical staining was used to assess ISGF-3 protein expression.
- Biopsies from patients with actinic keratosis and matched normal skin were analyzed.
- Expression levels were compared between premalignant lesions, SCC, and normal skin.
Main Results:
- A significant decrease in one or more ISGF-3 proteins was observed in 76% of actinic keratosis patients.
- Suppression of ISGF-3 proteins was confirmed in 67% of skin SCC patients.
- These findings suggest a pattern of declining ISGF-3 protein expression during skin cancer development.
Conclusions:
- Suppressed expression of ISGF-3 proteins is likely an early event in skin carcinogenesis.
- Reduced responsiveness to endogenous IFN due to ISGF-3 suppression may play a role in cancer development.
- These findings highlight the importance of IFN signaling pathways in skin premalignancy and SCC.
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