LOCALIZED PRODUCTION OF TGF-BETA MESSENGER-RNA IN TUMOR PROMOTER-STIMULATED MOUSE EPIDERMIS
LOCALIZED PRODUCTION OF TGF-BETA MESSENGER-RNA IN TUMOR PROMOTER-STIMULATED MOUSE EPIDERMIS
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DOI：
10.1038/331363a0
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发表时间：
1988-01-28
期刊：
影响因子：
64.8
通讯作者：
BALMAIN, A
中科院分区：
文献类型：
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作者：
AKHURST, RJ;FEE, F;BALMAIN, A
肿瘤启动子诱导广泛的形态学和生物化学的变化时，适用于小鼠表皮在体内1。这些包括在增殖和分化的不连续阶段诱导RNA（参考文献2）、DNA（参考文献3、4）和蛋白质合成5、6 7。这构成了一个理想的模型，用于研究TPA破坏表皮稳态及其随后重建的分子事件。转化生长因子-β（TGF-β）可诱导生长刺激、抑制或分化，具体取决于靶细胞8，9。已经提出了TGF-β在伤口愈合10和肿瘤促进11中的功能，但TGF-β的主要来源通常被认为是血小板、巨噬细胞或淋巴细胞8，并且该生长因子在体内调节组织稳态中的直接作用尚未得到证实。我们发现当肿瘤促进剂12-tetradecanoyl-phorbol-13-acetate（TPA）应用于小鼠皮肤时，在表皮细胞中诱导非常高水平的TGF-β信使RNA。原位杂交技术表明TGF-β合成的主要位点在基底上分化的表皮细胞中。这些结果表明，TGF-β可能是表皮稳态的天然调节剂，这在肿瘤促进中是重要的。
Tumour promoters induce a wide spectrum of morphological and biochemical alterations when applied to mouse epidermisin vivo1. These include the induction of RNA (ref. 2), DNA (refs 3, 4) and protein synthesis5,6during discrete phases of proliferation and differentiation7. This constitutes an ideal model for studying molecular events underlying the disruption of epidermal homeo-stasis by TPA, and its subsequent re-establishment. Transforming growth factor-β (TGF-β) can induce either growth stimulation, inhibition, or differentiation, depending on the target cell8,9. A function has been proposed for TGF-β in wound healing10and in tumour promotion11, but the main source of TGF-β is generally thought to be platelets, macrophages or lymphocytes8, and a direct role for this growth factor in regulating tissue homeostasis invivohas not been demonstrated. We show here that when the tumour promoter 12-tetradecanoyl-phorbol-13-acetate (TPA) is applied to the skin of mice, very high levels of TGF-β messenger RNA are induced in the epidermal cells.In situhybridization techniques show that the main site of TGF-β synthesis is in the suprabasal differentiating epidermal cells. These results suggest that TGF-β may be a natural regulator of epidermal homeostasis which is important in tumour promotion.