SELECTIVE-INHIBITION OF GROWTH-RELATED GENE-EXPRESSION IN MURINE KERATINOCYTES BY TRANSFORMING GROWTH FACTOR-BETA
SELECTIVE-INHIBITION OF GROWTH-RELATED GENE-EXPRESSION IN MURINE KERATINOCYTES BY TRANSFORMING GROWTH FACTOR-BETA
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DOI：
10.1128/mcb.8.8.3088
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发表时间：
1988-08-01
影响因子：
5.3
通讯作者：
MOSES, HL
中科院分区：
文献类型：
--
作者：
COFFEY, RJ;BASCOM, CC;MOSES, HL
转化生长因子β（TGF β）是上皮细胞增殖的有效抑制剂。一种非致瘤性表皮生长因子（EGF）依赖性上皮细胞系BALB/MK被TGF β可逆性地抑制生长。TGF.beta.也将消除静止BALB/MK细胞的EGF刺激的有丝分裂。增加的钙水平（> 1.0mM）将诱导BALB/MK细胞的分化;相反，TGF β-介导的生长抑制不导致诱导终末分化。在本研究中，TGF β的作用。和钙对生长因子诱导基因表达的影响。TGF.beta.在快速生长的BALB/MK细胞中显著降低c-myc和KC基因表达，并在静止细胞群中降低c-myc和KC的EGF诱导。TGF.beta.在转录后水平对c-myc表达进行调控，这种抑制作用依赖于蛋白质的合成。TGF.beta.对c-fos基因表达没有影响，而1.5 mM钙减弱静止细胞中EGF诱导的c-fos表达。β-的表达然而，在用TGF β处理的快速生长的和EGF再刺激的静止的BALB/MK细胞中，肌动蛋白略有增加。因此，在该系统中，TGF β.选择性降低某些与细胞增殖相关的基因（c-myc和KC）的表达，以及至少部分TGF β。作用是在转录后水平。
Transforming growth factor .beta. (TGF.beta.) is a potent inhibitor of epithelial cell proliferation. A nontumorigenic epidermal growth factor (EGF)-dependent epithelial cell line, BALB/MK, is reversibly growth arrested by TGF.beta.. TGF.beta. will also abrogate EGF-stimulated mitogenesis of quiescent BALB/MK cells. Increased levels of calcium (> 1.0 mM) will induce differentiation in BALB/MK cells; in contrast, TGF.beta.-mediated growth inhibition does not result in induction of terminal differentiation. In the present study, the effects of TGF.beta. and calcium on growth factor-inducible gene expression were examined. TGF.beta. markedly decreased c-myc and KC gene expression in rapidly growing BALB/MK cells and reduced the EGF induction of c-myc and KC in a quiescent population of cells. TGF.beta. exerted its control over c-myc expression at a posttranscriptional level, and this inhibitory effect was dependent on proteins synthesis. TGF.beta. had no effect on c-fos gene expression, whereas 1.5 mM calcium attenuated EGF-induced c-fos expression in quiescent cells. Expression of .beta.-actin, however, was slightly increased in both rapidly growing and EGF-restimulated quiescent BALB/MK cells treated with TGF.beta.. Thus, in this system, TGF.beta. selectively reduced expression of certain genes associated with cell proliferation (c-myc and KC), and at least part of the TGF.beta. effect was at a posttranscriptional level.