INVESTIGADORES
COLUCCIO LESKOW Federico
artículos
Título:
Leukemia inhibitory factor induces DNA synthesis in Swiss mouse 3T3 cells independently of cyclin D1 expression through a mechanism involving MEK/ERK1/2 activation.
Autor/es:
DEKANTY A; SAUANE M; CADENAS B; COLUCCIO F; BARRIO M; CASALA J; PACIENCIA M; ROGERS F; COSO OA; PIWIEN-PILIPUK G; RUDLAND PS; DE ASÚA LJ
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Referencias:
Año: 2006 p. 6136 - 6143
ISSN:
0021-9258
Resumen:
Leukemia inhibitory factor (LIF) and oncostatin M (OSM) induce DNA
synthesis in Swiss 3T3 cells through common signaling mechanism(s),
whereas other related cytokines such as interleukin-6 and ciliary
neurotrophic factor do not cause this response. Induction of DNA
replication by LIF or prostaglandin F2alpha (PGF2alpha) occurs, in
part, through different signaling events. LIF and OSM specifically
trigger STAT1 cytoplasmic to nuclear translocation, whereas PGF2alpha
fails to do so. However, LIF and PGF2alpha can trigger increases in
ERK1/2 activity, which are required for their mitogenic responses
because U0126, a MEK1/2 inhibitor, prevents both ERK1/2 activation and
induction of DNA synthesis by LIF or PGF2alpha treatment. PGF2alpha
induces cyclin D expression and full phosphorylation of retinoblastoma
protein. In contrast, LIF fails to promote increases in cyclin D
mRNA/protein levels; consequently, LIF induces DNA synthesis without
promoting full phosphorylation of retinoblastoma protein (Rb). However,
both LIF and PGF2alpha increase cyclin E expression. Furthermore, LIF
mitogenic action does not involve protein kinase C (PKC) activation,
because a PKC inhibitor does not block this effect. In contrast, PKC
activity is required for PGF2alpha mitogenic action. More importantly,
the synergistic effect between LIF and PGF2alpha to promote S phase
entry is independent of PKC activation. These results show fundamental
differences between LIF- and PGF2alpha-dependent mechanism(s) that
induce cellular entry into S phase. These findings are critical in
understanding how LIF and other related cytokine-regulated events
participate in normal cell cycle control and may also provide clues to
unravel crucial processes underlying cancerous cell division.