IL-2 signals through Sgk1 and inhibits proliferation and apoptosis in kidney cancer cells.
The interleukin-2 is a cytokine that is essential for lymphocytic survival and function. Ectopic expression of the IL-2 receptor in epithelial tissues has been reported previously, although the functional significance of this expression is still being investigated. We provided novel structural and functional information on the expression of the IL-2 receptor in kidney cancer cells and in other normal and neoplastic human epithelial tissues. In A-498 kidney cancer cells, we showed that IL-2 binding to its own receptor triggers a signal transduction pathway leading to the inhibition of proliferation and apoptosis. We found that the inhibition of proliferation is associated with Erk1/2 dephosphorylation, whereas the survival signals appear to be mediated by Sgk1 activation. This investigation focuses on the IL-2 induced regulation of Sgk1 and describes a role of the IL-2 receptor and Sgk1 in the regulation of epithelial tumor cell death and survival.
Amato
Rosario
R
Department of Experimental and Clinical Medicine G. Salvatore, University Magna Graecia, Campus Biomedico, Località Germaneto, Viale Europa, Catanzaro, 88100, Italy.
Menniti
Miranda
M
Agosti
Valter
V
Boito
Rosalia
R
Costa
Nicola
N
Bond
Heather M
HM
Barbieri
Vito
V
Tagliaferri
Pierosandro
P
Venuta
Salvatore
S
Perrotti
Nicola
N
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D015398:Signal Transduction; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D007376:Interleukin-2; D017346:Protein Serine-Threonine Kinases; D015375:Receptors, Interleukin-2; D000099184:Serum-Glucocorticoid Regulated Kinases