Resistance to inhibition of cell growth by transforming growth factor-beta and its role in oncogenesis.
Resistance to inhibition of cell growth by transforming growth factor-beta and its role in oncogenesis.
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发表时间：
1993
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通讯作者：
Fynan Tm;M. Reiss
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作者：
Fynan Tm;M. Reiss
转化生长因子-β（TGF β）首先被描述为在转化生长因子-α（TGF α）或表皮生长因子（EGF）存在下能够转化正常大鼠肾细胞的可溶性因子。现在已知TGF β具有广泛的作用，这取决于细胞类型，培养条件和其他生长因子的存在。尽管皮摩尔浓度的TGF β完全抑制大多数非恶性上皮细胞和早期造血祖细胞的生长，但对已发表的英文文献的综述表明，几乎所有上皮或造血来源的恶性细胞在体外对TGF β的抗增殖作用都是难治的。当与正常上皮细胞相比时，恶性癌细胞需要显著更高剂量的TGF β以实现类似程度的生长抑制，或者它们仅被大剂量的TGF β部分抑制。这种对TGF β敏感性的丧失与侵袭性的发展有关。似乎需要一个以上的遗传事件将敏感细胞转化为对TGF β完全不敏感的细胞。总之，在体外恶性转化过程中，对TGF β生长抑制作用的抵抗似乎是一个晚期但一致的事件。鉴定导致对TGF β反应丧失的遗传病变可能会导致设计新的治疗方式来阻止肿瘤生长。
Transforming growth factor-beta (TGF beta) was first described as a soluble factor capable of transforming normal rat kidney cells in the presence of transforming growth factor-alpha (TGF alpha) or epidermal growth factor (EGF). TGF beta is now known to have a wide spectrum of effects, depending on cell type, culture conditions, and the presence of other growth factors. Whereas picomolar concentrations of TGF beta completely inhibit the growth of most nonmalignant epithelial cells and early hematopoietic progenitor cells, a review of the published English language literature reveals that virtually all malignant cells of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF beta in vitro. When compared with normal epithelial cells, malignant carcinoma cells require significantly higher doses of TGF beta to achieve a similar degree of growth suppression or they are only partially suppressed by large doses of TGF beta. This loss of sensitivity to TGF beta is associated with the development of invasive properties. More than one genetic event appears to be required to convert a sensitive cell into one that is completely refractory to TGF beta. In conclusion, resistance to the growth-inhibiting effect of TGF beta appears to be a late but consistent event in the process of malignant transformation in vitro. Identification of the genetic lesions that result in the loss of response to TGF beta may lead to the design of new therapeutic modalities to arrest tumor growth.