title: Role for Id-1 in immunobiology of normal keratinocytes and in basal cell carcinoma.
abstract: It has been established that Id proteins can block the basic helix-loop-helix (HLH) transcription factors, thereby impacting the onset of senescence in keratinocytes, as well as influencing tumorigenesis involving squamous cell carcinomas. However, the ability of Id-1 to influence the immunologic response of epithelial cells to cytokines implicated in cutaneous oncology such as gamma interferon (IFN-gamma) has not been determined. Using a whole population of human keratinocytes infected with a retrovirus to induce over-expression of Id-1, the influence on early differentiation of rapidly proliferating keratinocytes was assessed, as was the response to IFN-gamma. While induction of involucrin, a marker of early differentiation, was not altered in Id-1 overexpressing keratinocytes, the IFN-gamma mediated increase in intercellular adhesion molecule-1 (ICAM-1) and HLA-DR was reduced. No change in constitutive or inducible levels of MHC class I antigen, CD95 (Fas antigen) or LFA-3 (CD58) was observed in this system. Immunostaining and Western blot analysis revealed over-expression of Id-1 in basal cell carcinomas (BCCs). These tumors not only strongly and diffusely expressed Id-1, but were also characterized by reduced ICAM-1 and HLA-DR expression. Thus, dysregulated Id-1 may not only contribute to delaying the senescence program in keratinocytes, it may also contribute to the escape of the relatively undifferentiated tumor cells in BCC from immune surveillance.
authors.affiliation: Department of Pathology, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL, USA.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Chaturvedi
authors.forename: Brian
authors.initials: B
authors.lastname: Bonish
authors.forename: Patricia
authors.initials: P
authors.lastname: Bacon
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Qin
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Denning
authors.forename: Kimberly
authors.initials: K
authors.lastname: Foreman
authors.forename: Manuel O
authors.initials: MO
authors.lastname: Diaz
authors.forename: June
authors.initials: J
authors.lastname: Robinson
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nickoloff
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002280:Basal Cell Carcinoma / Q000276:immunology*; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology*; D012097:Repressor Proteins; D012878:Skin Neoplasms / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006684:HLA-DR Antigens; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma