Role for Id-1 in immunobiology of normal keratinocytes and in basal cell carcinoma.
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.
Chaturvedi
Vijaya
V
Department of Pathology, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL, USA.
Bonish
Brian
B
Bacon
Patricia
P
Qin
Jian-Zhong
JZ
Denning
Mitchell F
MF
Foreman
Kimberly
K
Diaz
Manuel O
MO
Robinson
June
J
Nickoloff
Brian J
BJ
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
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