Cell-mediated co-action of transforming growth factors: incubation of type beta with normal rat kidney cells produces a soluble activity that prolongs the ruffling response to type alpha.
Cell-mediated co-action of transforming growth factors: incubation of type beta with normal rat kidney cells produces a soluble activity that prolongs the ruffling response to type alpha.
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细胞介导的转化生长因子的共同作用：β型与正常大鼠肾细胞的孵育产生可溶性活性，从而延长对α类型的皱纹反应。
DOI：
10.1083/jcb.102.4.1230
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发表时间：
1986-04
影响因子：
7.8
通讯作者：
Auersperg, N
中科院分区：
文献类型：
--
作者：
Myrdal, S E;Twardzik, D R;Auersperg, N
强烈的、持续的皱褶是许多转化细胞的特征，但未转化的细胞仅在暴露于生长因子后短暂地强烈皱褶。我们以前报道过，由Kirsten鼠肉瘤病毒转化的正常大鼠肾（NRK）细胞系的细胞分泌它们自己的皱褶诱导剂，这些皱褶诱导剂在它们自身或未转化的NRK细胞中引起持续皱褶。在本研究中，我们研究了转化生长因子TGF-α和TGF-β在未转化的NRK细胞中诱导和维持皱褶的作用，并观察到以下结果：TGF-α引起了短暂的表皮生长因子（EGF）样反应，这可以通过细胞预先暴露于EGF或针对TGF-α COOH末端的抗血清来阻断。TGF-β不引起皱褶，并且本身不延长TGF-α皱褶。一种新的，缓冲液可溶性（可转移）介质活动产生的TGF-β与NRK细胞孵育6小时延长了最大TGF-α诱导的皱褶的持续时间几倍。这项研究表明，TGF-α单独引起EGF样的，短暂的皱褶反应，但既不是TGF-α或TGF-β单独，也不是两者一起，引起转化相关的持续皱褶。相反，TGF-α与一种新的TGF-β依赖性活性协同作用。这种新的活性似乎抑制TGF-α诱导的皱褶的正常细胞失调。抑制生长因子应答的细胞失调可能在与恶性肿瘤相关的不受调节的生长中起关键作用。
Intense, continuous ruffling is a characteristic of many transformed cells, but untransformed cells ruffle intensely only briefly after exposure to growth factors. We reported previously that cells of a normal rat kidney (NRK) cell line transformed by Kirsten murine sarcoma virus secrete their own ruffle-inducing agent(s) that cause sustained ruffling in either themselves or untransformed NRK cells. In the present study, we examined the roles of the transforming growth factors TGF-alpha and TGF-beta in the induction and maintenance of ruffling in untransformed NRK cells and observed the following: TGF-alpha caused a transient epidermal growth factor (EGF)-like response, which could be blocked by prior exposure of cells to EGF or by antiserum directed against the COOH-terminus of TGF-alpha. TGF-beta caused no ruffling and did not itself prolong TGF-alpha ruffling. A new, buffer-soluble (transferable) mediator activity produced by incubation of TGF-beta with NRK cells for 6-h extended the duration of maximal TGF-alpha- induced ruffling by several-fold. This study demonstrates that TGF- alpha alone causes an EGF-like, transient ruffling response, but neither TGF-alpha or TGF-beta alone, nor the two together, cause transformation-associated sustained ruffling. Rather, TGF-alpha acts in concert with a new, TGF-beta-dependent activity. This new activity appears to inhibit normal cellular off-regulation of TGF-alpha-induced ruffling. Inhibition of the cellular off-regulation of a growth factor response could play a key role in the unregulated growth associated with malignancy.