title: Expression of protein mediators of type I interferon signaling in human squamous cell carcinoma of the skin.
abstract: 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) 1alpha/beta, STAT2, p48, STAT3a, and STAT3beta, 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 (STAT1alpha/beta, STAT2, and p48) and STAT3alpha and STAT3beta mediators of IFN-alpha/beta 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.
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. jclifford@notes.mdacc.tmc.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Clifford
authors.forename: D G
authors.initials: DG
authors.lastname: Menter
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Walch
authors.forename: C
authors.initials: C
authors.lastname: Zou
authors.forename: G L
authors.initials: GL
authors.lastname: Clayman
authors.forename: T S
authors.initials: TS
authors.lastname: Schaefer
authors.forename: A K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: R
authors.initials: R
authors.lastname: Lotan
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000378:metabolism*; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors