This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clifford, J. L. Articles by Lippman, S. M. Search for Related Content PubMed PubMed Citation Articles by Clifford, J. L. Articles by Lippman, S. M.

Expression of Protein Mediators of Type I Interferon Signaling in Human Squamous Cell Carcinoma of the Skin¹

Departments of Clinical Cancer Prevention [J. L. C., D. G. M., X. Y., E. W., C. Z., S. M. L.], Neurosurgery [T. S. S.], Pathology [A. K. E.], Head and Neck Surgery [G. L. C.], and Thoracic/Head and Neck Medical Oncology [R. L.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

IFN-based therapy has been shown to be active in the treatment of squamous cell carcinoma (SCC) of the skin and has promise for chemoprevention and treatment of several other cancers. In an effort to better understand the molecular mechanism of this activity, we have determined the expression pattern of several of the protein mediators of type I IFN signaling by immunohistochemistry in cutaneous SCC, SCC metastases, and adjacent nonmalignant epithelium from patient biopsies. All of the proteins, signal transducer and activator of transcription (STAT) 1/ß, STAT2, p48, STAT3, and STAT3ß, are expressed at varying levels in the adjacent epidermis, as well as in other epidermal and dermal cell types. For the majority of samples tested, the expression of one or more of these proteins was reduced in SCC primary tumors compared with the adjacent nonmalignant epithelial cells, as determined by manual scoring. Quantitative densitometry of several samples revealed differences that are statistically significant. Our study provides the first direct evidence for the expression of the IFN-stimulated gene factor 3 (STAT1/ß, STAT2, and p48) and STAT3 and STAT3ß mediators of IFN-/ß signaling in human skin and skin-derived SCCs. These data have led to the hypothesis that the loss of IFN sensitivity may contribute to the development and progression of skin SCC.

This article has been cited by other articles:

				J. L. Clifford, X. Yang, E. Walch, M. Wang, and S. M. Lippman Dominant Negative Signal Transducer and Activator of Transcription 2 (STAT2) Protein: Stable Expression Blocks Interferon {alpha} Action in Skin Squamous Cell Carcinoma Cells Mol. Cancer Ther., May 1, 2003; 2(5): 453 - 459. [Abstract] [Full Text] [PDF]

				J. L. Clifford, E. Walch, X. Yang, X. Xu, D. S. Alberts, G. L. Clayman, A. K. El-Naggar, R. Lotan, and S. M. Lippman Suppression of Type I Interferon Signaling Proteins Is an Early Event in Squamous Skin Carcinogenesis Clin. Cancer Res., July 1, 2002; 8(7): 2067 - 2072. [Abstract] [Full Text] [PDF]

				E. E.W. Cohen and E. E. Vokes Searching for a Standard J. Clin. Oncol., January 15, 2002; 20(2): 359 - 361. [Full Text] [PDF]

				D. M. Shin, B. S. Glisson, F. R. Khuri, J. L. Clifford, G. Clayman, S. E. Benner, A. A. Forastiere, L. Ginsberg, D. Liu, J. J. Lee, et al. Phase II and Biologic Study of Interferon Alfa, Retinoic Acid, and Cisplatin in Advanced Squamous Skin Cancer J. Clin. Oncol., January 15, 2002; 20(2): 364 - 370. [Abstract] [Full Text] [PDF]

				W. K. Hong, M. R. Spitz, and S. M. Lippman Cancer Chemoprevention in the 21st Century: Genetics, Risk Modeling, and Molecular Targets J. Clin. Oncol., November 1, 2000; 18(90001): 9s - 18. [Full Text] [PDF]