Expression profiles and functional implications of p53-like transcription factors in thymic epithelial cell subtypes.
In this study, we investigated the localization and functional significance of p53 tumor suppressor-like molecules, p63 and p73, in human thymic epithelial cells (TECs). Immunohistochemical studies showed particular distribution profiles of p63 and p73 in thymic epithelium, in which cortical TECs preferentially expressed p63 in their nuclei whereas subcapsular and medullary TECs expressed both p63 and p73 in their nuclei. The wide distribution of p63 in TECs was further suggested by studies using TECs of primary culture. In vitro studies using two human TEC lines demonstrated that p63 was capable of up-regulating intercellular adhesion molecule-1 (ICAM-1) and enhancing the production of IL-6 and IL-8. Moreover, in vitro studies also indicated that p73, but not p63, had the capacity to induce granulocyte macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) in the TEC lines. These findings suggest that p63 would regulate the cell adhesive property through ICAM-1/LFA-1 interaction and the production of IL-6 and IL-8, probably in all TEC subtypes. p73 in subcapslar and medullary TECs was suggested to play a role in the regulation of the production of GM-CSF and G-CSF, which might stimulate other stromal cells such as dendritic cells, macrophages and endothelial cells around these regions.
Kikuchi
Tomoki
T
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Ichimiya
Shingo
S
Kojima
Takashi
T
Crisa
Laura
L
Koshiba
Shigeru
S
Tonooka
Akiko
A
Kondo
Nobuhiko
N
Van Der Saag
Paul T
PT
Yokoyama
Shigeaki
S
Sato
Noriyuki
N
D002460:Cell Line; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013950:Thymus Gland / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D016207:Cytokines; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D018799:Intercellular Adhesion Molecule-1