Henttu P, Vihko P
Biocenter, University of Oulu, Finland.
Cancer Res. 1993 Mar 1;53(5):1051-8.
In order to characterize the effects of growth factors on the regulation of expression of the genes coding for prostatic differentiation markers, prostatic acid phosphatase and prostate-specific antigen, we studied changes occurring in the biosynthesis of these enzymes in LNCaP prostatic cancer cells treated with growth factors. Epidermal growth factor was found to reduce the secretion of prostatic acid phosphatase and prostate-specific antigen by the cells, as the result of lowered steady-state levels of the corresponding messenger RNAs (mRNAs). In addition, epidermal growth factor (EGF) interfered with the androgen regulation of these genes. EGF evoked these changes in a concentration- and time-dependent fashion, in both the presence and absence of serum and most likely through interactions with the epidermal growth factor receptor, inasmuch as similar effects were achieved by treating the cells with transforming growth factor alpha. The regulation of the human glandular kallikrein 1 gene was quite similar to the regulation of the prostate-specific antigen gene. In addition to the expression of the genes coding for prostatic secretory proteins, the amount of the human androgen receptor mRNA was down-regulated by EGF. This reduction was more pronounced than the autologous down-regulation of human androgen receptor (hAR) mRNA by androgen and could be maintained for at least 5 days. In the presence of androgen, some of the effects of EGF and transforming growth factor alpha on the levels of androgen-regulated mRNAs may be due to down-regulation of the expression of the hAR gene. Transforming growth factor beta 1, which blocked the growth induction of LNCaP cells by EGF, increased the level of prostatic acid phosphatase and hAR mRNAs, but when given to the cells together with EGF its up-regulatory effect could not be discerned. In summary, regulation of the prostatic acid phosphatase and prostate-specific antigen genes is a complex matter, inasmuch as androgens and growth factors regulate the levels of the mRNAs originating from them. Furthermore, the interactions between the androgen-regulatory system and the growth factor-regulatory systems are likely to be at multiple levels in prostatic cells, as suggested by the modulation of the hAR gene expression by these growth factors.
为了描述生长因子对前列腺分化标志物、前列腺酸性磷酸酶和前列腺特异性抗原编码基因表达调控的影响，我们研究了用生长因子处理的LNCaP前列腺癌细胞中这些酶生物合成的变化。发现表皮生长因子可降低细胞分泌前列腺酸性磷酸酶和前列腺特异性抗原，这是相应信使核糖核酸（mRNA）稳态水平降低的结果。此外，表皮生长因子（EGF）干扰了这些基因的雄激素调节。EGF以浓度和时间依赖性方式引发这些变化，无论有无血清，且很可能是通过与表皮生长因子受体相互作用，因为用转化生长因子α处理细胞也能产生类似效果。人腺激肽释放酶1基因的调控与前列腺特异性抗原基因的调控非常相似。除了前列腺分泌蛋白编码基因的表达外，人雄激素受体mRNA的量也被EGF下调。这种下调比雄激素对人雄激素受体（hAR）mRNA的自身下调更明显，并且可以维持至少5天。在有雄激素存在的情况下，EGF和转化生长因子α对雄激素调节的mRNA水平的一些影响可能是由于hAR基因表达的下调。转化生长因子β1可阻断EGF对LNCaP细胞的生长诱导作用，增加前列腺酸性磷酸酶和hAR mRNA的水平，但与EGF同时给予细胞时，其上调作用无法辨别。总之，前列腺酸性磷酸酶和前列腺特异性抗原基因的调控是一个复杂的问题，因为雄激素和生长因子调节源自它们的mRNA水平。此外，正如这些生长因子对hAR基因表达的调节所表明的那样，雄激素调节系统和生长因子调节系统之间的相互作用可能在前列腺细胞中处于多个水平。
