Sh. Park et al., Mechanism of induction of transforming growth factor-beta type II receptorgene expression by v-Src in murine myeloid cells, CELL GROWTH, 12(1), 2001, pp. 9-18
Transforming growth factor (TGF)-beta1 plays an important role during hemat
opoiesis. Previously, we had shown that the growth of a v-Src-transformed m
yeloid cell line was markedly more inhibited by TGF-beta treatment when com
pared with the wild-type myeloid cell line. To investigate the increased gr
owth sensitivity of the v-Src-transformed myeloid cell line, 32D-src, to TG
F-beta, we examined expression of the TGF-beta type II receptor (TGF-beta R
II) gene in myeloid cell lines. Northern blot analysis showed that expressi
on of similar to8- and 6-kb species of TGF-beta RII transcripts was markedl
y increased in the 32D-src cell line. The expression of the TGF-beta RII pr
omoter linked to a reporter gene was increased 23-fold by v-Src, DNA transf
ection and electrophoretic mobility shift assay revealed that v-Src induces
TGF-beta RII promoter activity through an AP1/ATF2-like sequence (-219 to
-172), ETS binding sites (+1 to +36), and the inverted CCAAT box (-81 to -7
7), Novel DNA-protein complexes with FTS binding sites are significantly in
creased in v-src-transformed cell lines compared with the control cell line
. These results suggest that v-Src induces activity of the TGF-beta RII pro
moter through multiple elements by inducing expression of nuclear proteins
interacting with these elements.