Moses H L, Yang E Y, Pietenpol J A
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Ciba Found Symp. 1991;157:66-74; discussion 75-80. doi: 10.1002/9780470514061.ch5.
The closely related mammalian TGF-betas (TGF-beta 1, TGF-beta 2 and TGF-beta 3) are potent inhibitors of proliferation of many cell types in vitro. TGF-beta 1 has been demonstrated to be growth inhibitory in vivo for epithelial, endothelial, myeloid and lymphoid cells. Utilizing skin keratinocytes as a model system for studying the mechanism of TGF-beta 1-induced growth inhibition, it has been demonstrated that TGF-beta 1 rapidly inhibits transcription of the c-myc gene. Antisense c-myc oligonucleotides inhibit proliferation of keratinocytes as effectively as does TGF-beta 1, indicating that TGF-beta 1 suppression of c-myc expression is an important component of this growth inhibition. Studies utilizing DNA tumour virus transforming gene constructs have shown that the retinoblastoma gene product, pRb, or a related protein, is needed for TGF-beta 1 suppression of c-myc transcription. Thus, TGF-beta 1 may act through a tumour suppressor gene product, pRb, to suppress transcription of a proto-oncogene, c-myc, and subsequently inhibit cell proliferation.
密切相关的哺乳动物转化生长因子β（转化生长因子β1、转化生长因子β2和转化生长因子β3）在体外是多种细胞类型增殖的有效抑制剂。转化生长因子β1已被证明在体内对上皮细胞、内皮细胞、髓样细胞和淋巴细胞具有生长抑制作用。利用皮肤角质形成细胞作为研究转化生长因子β1诱导生长抑制机制的模型系统，已证明转化生长因子β1能迅速抑制c-myc基因的转录。反义c-myc寡核苷酸抑制角质形成细胞增殖的效果与转化生长因子β1相同，表明转化生长因子β1对c-myc表达的抑制是这种生长抑制的重要组成部分。利用DNA肿瘤病毒转化基因构建体进行的研究表明，转化生长因子β1抑制c-myc转录需要视网膜母细胞瘤基因产物pRb或相关蛋白。因此，转化生长因子β1可能通过肿瘤抑制基因产物pRb发挥作用，抑制原癌基因c-myc的转录，进而抑制细胞增殖。
