Interleukin-7 and interleukin-15 regulate the expression of the bcl-2 and c-myb genes in cutaneous T-cell lymphoma cells.
Interleukin-7 (IL-7) and IL-15 have been recently identified as growth factors for cutaneous T-cell lymphoma (CTCL) cells, and they protect these cells from cell death. Using the CTCL cell line SeAx as a test system now shows that IL-7 and IL-15 are indeed necessary to maintain high levels of bcl-2. The up-regulation of bcl-2 was paralleled by increased DNA-binding activities of the transcription factors STAT2, STAT5, STAT6, and c-Myb to bcl-2 gene promoter-enhancer elements. Because STAT5 and c-Myb positively regulate bcl-2, IL-7 and IL-15 may mediate some of their effects on cell death survival gene expression through these 2 factors. Constitutive activities of the 3 STAT factors and c-Myb were found in the IL-7- and IL-15-independent CTCL cell lines HUT78 and MyLa 2059. The c-Myb protein was also present in CTCL cells of the skin lesions of all investigated patients. These results indicate that IL-7 and IL-15 may increase bcl-2 expression in CTCL cells by the activation of c-myb and STAT factors.
Qin
J Z
JZ
Department of Dermatology, University Hospital of Zurich, Switzerland.
Zhang
C L
CL
Kamarashev
J
J
Dummer
R
R
Burg
G
G
Döbbeling
U
U
D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics*; D020570:Genes, myb / Q000235:genetics*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology* / Q000502:physiology; D015851:Interleukin-7 / Q000494:pharmacology* / Q000502:physiology; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000473:pathology; D008894:Milk Proteins; D011485:Protein Binding / Q000187:drug effects; D020598:Proto-Oncogene Proteins c-myb / Q000187:drug effects / Q000378:metabolism; D050795:STAT2 Transcription Factor; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D019409:Interleukin-15; D015851:Interleukin-7; D008894:Milk Proteins; D020598:Proto-Oncogene Proteins c-myb; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators