ii) A
central role for Stat3 in IL-6-induced regulation of growth and
differentiation in M1 leukemia cells. Nakajima-K; Yamanaka-Y;
Nakae-K; Kojima-H; Ichiba-M; Kiuchi-N; Kitaoka-T; Fukada-T; Hibi-M;
Hirano-T, EMBO-J. 1996 Jul 15; 15(14): 3651-8ii) A
central role for Stat3 in IL-6-induced regulation of growth and
differentiation in M1 leukemia cells. Nakajima-K; Yamanaka-Y;
Nakae-K; Kojima-H; Ichiba-M; Kiuchi-N; Kitaoka-T; Fukada-T; Hibi-M;
Hirano-T, EMBO-J. 1996 Jul 15; 15(14): 3651-8
Interleukin-6 (IL-6) induces either differentiation or growth of a
variety of cells. Little is known about the molecular basis of this
cellular decision. The family of signal transducer and activator of
transcription (Stat) proteins are involved in signaling through a
variety of cytokine and growth factor receptors, although their
biological roles have not been established. To address whether Stat
proteins play roles in IL-6-induced growth or differentiation, we
introduced two types of mutant Stat3 acting in a dominant-negative
manner into M1 leukemic cells which respond to IL-6 with growth
arrest and terminal differentiation. We show that dominant-negative
forms of Stat3 inhibited both IL-6-induced growth arrest at G(0)/G1
and macrophage differentiation in the M1 transformants. Blocking of
Stat activation resulted in inhibition of IL-6-induced repression of
c-myb and c-myc. Furthermore, IL-6 enhanced the growth of M1 cells
primarily through shortening the length of the G1 period when Stat3
was suppressed. Thus IL-6 generates both growth-enhancing signals and
growth arrest- and differentiation-inducing signals at the same time.
Stat3 may be a key molecule which determines the cellular decision
from cell growth to differentiation in M1 cells.
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