Park S H, Birchenall-Roberts M C, Yi Y, Lee B I, Lee D K, Bertolette D C, Fu T, Ruscetti F, Kim S J
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA.
Cell Growth Differ. 2001 Jan;12(1):9-18.
Transforming growth factor (TGF)-beta1 plays an important role during hematopoiesis. Previously, we had shown that the growth of a v-Src-transformed myeloid cell line was markedly more inhibited by TGF-beta treatment when compared with the wild-type myeloid cell line. To investigate the increased growth sensitivity of the v-Src-transformed myeloid cell line, 32D-src, to TGF-beta, we examined expression of the TGF-beta type II receptor (TGF-beta RII) gene in myeloid cell lines. Northem blot analysis showed that expression of approximately 8- and 6-kb species of TGF-beta RII transcripts was markedly increased in the 32D-src cell line. The expression of the TGF-beta RII promoter linked to a reporter gene was increased 23-fold by v-Src. DNA transfection 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 -77). Novel DNA-protein complexes with ETS binding sites are significantly increased 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 promoter through multiple elements by inducing expression of nuclear proteins interacting with these elements.
转化生长因子（TGF）-β1在造血过程中发挥重要作用。此前，我们已经表明，与野生型髓系细胞系相比，TGF-β处理对v-Src转化的髓系细胞系的生长抑制作用明显更强。为了研究v-Src转化的髓系细胞系32D-src对TGF-β的生长敏感性增加的原因，我们检测了髓系细胞系中TGF-βⅡ型受体（TGF-βRII）基因的表达。Northern印迹分析表明，32D-src细胞系中约8 kb和6 kb的TGF-βRII转录本的表达明显增加。与报告基因相连的TGF-βRII启动子的表达因v-Src而增加了23倍。DNA转染和电泳迁移率变动分析表明，v-Src通过AP1/ATF2样序列（-219至-172）、ETS结合位点（+1至+36）和反向CCAAT框（-
