CONTROL OF JUNB AND EXTRACELLULAR-MATRIX PROTEIN EXPRESSION BY TRANSFORMING GROWTH FACTOR-BETA-1 IS INDEPENDENT OF SIMIAN VIRUS-40 T-ANTIGEN-SENSITIVE GROWTH-INHIBITORY EVENTS
CONTROL OF JUNB AND EXTRACELLULAR-MATRIX PROTEIN EXPRESSION BY TRANSFORMING GROWTH FACTOR-BETA-1 IS INDEPENDENT OF SIMIAN VIRUS-40 T-ANTIGEN-SENSITIVE GROWTH-INHIBITORY EVENTS
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DOI：
10.1128/mcb.11.2.972
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发表时间：
1991-02-01
影响因子：
5.3
通讯作者：
MASSAGUE, J
中科院分区：
文献类型：
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作者：
LAIHO, M;RONNSTRAND, L;MASSAGUE, J
用转化生长因子-β-1（TGF-β-1）处理Mv 1 Lu貂肺上皮细胞可防止视网膜母细胞瘤易感基因产物RB在细胞周期G1期晚期的磷酸化，这被认为可使RB保持在生长抑制状态。 这种作用被G1晚期的细胞周期阻滞所抵消（M. Laiho，J. A.德卡普里奥卢德洛，D. M.利文斯顿和J. Massague，Cell 62：175-185，1990）。 可以通过猴病毒40 T抗原的表达来防止逮捕，该抗原结合磷酸化不足的RB，推测阻断其生长抑制活性。 然而，细胞对TGF-β-1的反应是复杂的，包括编码核转录因子和细胞外基质组分的基因表达水平的变化。 为了确定TGF-β-1反应的各个组成部分之间的关系，我们研究了TGF-β-1对细胞的作用，T抗原阻止了对该因子的生长抑制反应。 TGF-β-1除了指数增长的Mv 1 Lu细胞的junB mRNA和三个细胞外基质蛋白质：纤溶酶原激活物抑制剂-1，纤连蛋白和血小板反应蛋白的水平增加。 在动力学上，对junB和纤溶酶原激活物抑制剂-1表达的影响发生得更快（在1至2小时达到半最大值），而对纤连蛋白和血小板反应蛋白表达的影响（在6至10小时达到半最大值）。 这些影响之前或重叠，分别从细胞周期的Mv 1 Lu细胞撤出。 然而，在Mv 1 Lu细胞中表达转染的T抗原基因并不能阻止对TGF-β 1的任何反应。 结果表明，TGF-β-1刺激的JunB和细胞外基质蛋白在Mv 1 Lu细胞中的表达可以独立于导致生长停滞的T抗原敏感性事件发生。
Treatment of Mv1Lu mink lung epithelial cells with transforming growth factor-beta-1 (TGF-beta-1) prevents phosphorylation of the retinoblastoma susceptibility gene product, RB, in late G1 phase of the cell cycle, which is thought to retain RB in a growth-suppressive state. This effect is paralleled by cell cycle arrest in late G1 (M. Laiho, J. A. DeCaprio, J. W. Ludlow, D. M. Livingston, and J. Massague, Cell 62:175-185, 1990). Arrest can be prevented by expression of simian virus 40 T antigen, which binds to underphosphorylated RB, presumably blocking its growth-suppressive activity. The response of cells to TGF-beta-1, however, is complex and includes changes in the levels of expression of genes encoding nuclear transcription factors and extracellular matrix components. To define the relationships among various components of the TGF-beta-1 response, we have investigated the effect of TGF-beta-1 on cells whose growth-inhibitory response to this factor is prevented by T antigen. TGF-beta-1 addition to exponentially growing Mv1Lu cells increased the levels of junB mRNA and of three extracellular matrix proteins: plasminogen activator inhibitor-1, fibronectin, and thrombospondin. Kinetically, the effects on junB and plasminogen activator inhibitor-1 expression occurred faster (half-maximal at 1 to 2 h) than the effects on fibronectin and thrombospondin expression (half-maximal at 6 to 10 h). These effects either preceded or overlapped, respectively, the withdrawal of Mv1Lu cells from the cell cycle. Expression of a transfected T-antigen gene in Mv1Lu cells, however, did not prevent any of these responses to TGF-beta-1. The results indicate that TGF-beta-1-stimulated expression of junB and extracellular matrix proteins in Mv1Lu cells can occur independently of the T-antigen-sensitive events that lead to growth arrest.