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.
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 SCCpatients 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.
Authors: Ana M Gamero; Matthew R Young; Roycelynn Mentor-Marcel; Gerd Bobe; Anthony J Scarzello; Jennifer Wise; Nancy H Colburn Journal: Cancer Prev Res (Phila) Date: 2010-03-16
Authors: Chanyu Yue; Jun Xu; Marc Daryl Tan Estioko; Kevin P Kotredes; Yolanda Lopez-Otalora; Brendan A Hilliard; Darren P Baker; Stefania Gallucci; Ana M Gamero Journal: Int J Cancer Date: 2014-06-17 Impact factor: 7.396
Authors: Zanobia A Syed; Weihong Yin; Kendall Hughes; Jennifer N Gill; Runhua Shi; John L Clifford Journal: BMC Cancer Date: 2011-05-19 Impact factor: 4.430