Wild-type p53-mediated down-modulation of interleukin 15 and interleukin 15 receptors in human rhabdomyosarcoma cells.
We recently reported that rhabdomyosarcoma cell lines express and secrete interleukin 15 (IL-15), a tightly regulated cytokine with IL-2-like activity. To test whether the p53-impaired function that is frequently found in this tumour type could play a role in the IL-15 production, wild-type p53 gene was transduced in the human rhabdomyosarcoma cell line RD (which harbours a mutated p53 gene), and its effect on proliferation and expression of IL-15 was studied. Arrest of proliferation was induced by wild-type p53; increased proportions of G1-arrested cells and of apoptotic cells were observed. A marked down-modulation of IL-15 expression, at both the mRNA and protein level, was found in p53-transduced cells. Because a direct effect of IL-15 on normal muscle cells has been reported, the presence of IL-15 membrane receptors was studied by cytofluorometric analysis. Rhabdomyosarcoma cells showed IL-15 membrane receptors, which are down-modulated by wild-type p53 transfected gene. In conclusion, wild-type p53 transduction in human rhabdomyosarcoma cells induces the down-modulation of both IL-15 production and IL-15 receptor expression.
De Giovanni
C
C
Cancer Research Institute, University of Bologna, Italy.
Nanni
P
P
Sacchi
A
A
Soddu
S
S
Manni
I
I
D'Orazi
G
G
Bulfone-Paus
S
S
Pohl
T
T
Landuzzi
L
L
Nicoletti
G
G
Frabetti
F
F
Rossi
I
I
Lollini
P L
PL
D002455:Cell Division / Q000235:genetics; D019070:Cell Lineage; D015536:Down-Regulation; D016158:Genes, p53; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
C508024:IL15RA protein, human; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2