OVEREXPRESSION OF THE C-MYC ONCOPROTEIN BLOCKS THE GROWTH-INHIBITORY RESPONSE BUT IS REQUIRED FOR THE MITOGENIC EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-1
OVEREXPRESSION OF THE C-MYC ONCOPROTEIN BLOCKS THE GROWTH-INHIBITORY RESPONSE BUT IS REQUIRED FOR THE MITOGENIC EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-1
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DOI：
10.1073/pnas.92.8.3239
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发表时间：
1995-04-11
影响因子：
11.1
通讯作者：
MOSES, HL
中科院分区：
文献类型：
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作者：
ALEXANDROW, MG;KAWABATA, M;MOSES, HL
转化生长因子 β 1 (TGF β 1) 更有趣的方面之一是它既可以作为某些间充质细胞的有丝分裂因子，又可以作为淋巴、内皮和上皮细胞的有效生长抑制剂。数据表明，c-myc 可能在 TGF beta 1 的促有丝分裂和抗增殖作用中发挥关键作用。与先前使用组成型表达外源 c-myc cDNA 的 C3H/10T1/2 成纤维细胞的研究一致，我们表明表达嵌合雌激素诱导形式的 c-myc (mycER) 的 AKR-2B 成纤维细胞能够在软组织中形成集落。仅当 c-myc 被激素激活时，才在存在 TGF beta 1 的琼脂上进行。虽然这些发现支持 c-myc 在 TGF beta 1 的有丝分裂反应中发挥协同作用，但我们还发现 c-myc 可以拮抗 TGF beta 1 的生长抑制反应。通常被 TGF beta 1 抑制生长的小鼠角质形成细胞 (BALB/MK) 在 mycER 激活后对 TGF beta 1 的生长抑制作用变得不敏感。研究发现，只有在 G(1) 早期用激素诱导融合蛋白时，mycER 激活才能阻断 TGF beta 1 诱导的生长停滞。在G(1)后期添加雌二醇对TGFβ(1)诱导的生长抑制没有抑制作用。
One of the more intriguing aspects of transforming growth factor beta 1 (TGF beta 1) is its ability to function as both a mitogenic factor for certain mesenchymal cells and a potent growth inhibitor of lymphoid, endothelial, and epithelial cells. Data are presented indicating that c-myc may play a pivotal role in both the mitogenic and antiproliferative actions of TGF beta 1. In agreement with previous studies using C3H/10T1/2 fibroblasts constitutively expressing an exogenous c-myc cDNA, we show that AKR-2B fibroblasts expressing a chimeric estrogen-inducible form of c-myc (mycER) are able to form colonies in soft agar in the presence of TGF beta 1 only when c-myc is activated by hormone. Whereas these findings support a synergistic role for c-myc in mitogenic responses to TGF beta 1, we also find that c-myc can antagonize the growth-inhibitory response to TGF beta 1. Mouse keratinocytes (BALB/MK), which are normally growth-arrested by TGF beta 1, are rendered insensitive to the growth-inhibitory effects of TGF beta 1 upon mycER activation. This ability of mycER activation to block TGF beta 1-induced growth arrest was found to occur only when the fusion protein was induced with hormone in the early part of G(1). Addition of estradiol late in G(1) had no suppressive effect on TGF beta(1)-induced growth inhibition.