Carruba G, Pfeffer U, Fecarotta E, Coviello D A, D'Amato E, Lo Castro M, Vidali G, Castagnetta L
Hormone Biochemistry Laboratories, Medical School, University of Palermo, Italy.
Cancer Res. 1994 Mar 1;54(5):1190-3.
Significant inhibition of proliferative activity in PC3 human prostate cancer cells by estradiol is reported, accompanied by experimental evidence for a specific estrogen receptor (ER). Radioligand-binding assays revealed the presence of high affinity sites of estrogen binding in the nuclear compartment of PC3 cells. In addition, using a reverse transcriptase-polymerase chain reaction system, we obtained evidence of either normal or a variant ER mRNA; the latter, which lacks the entire exon 4, is coexpressed with normal ER mRNA and has been recently characterized in our laboratories. The likelihood that the inhibitory effect exerted by estradiol could be mediated by an increase of transforming growth factor beta (TGF beta) production was also investigated. Use of monoclonal antibodies against TGF beta 1 produced a 3-fold increase of growth rate in PC3 cells; this clearly speaks for high levels of endogenous TGF beta 1. This effect was almost completely abolished after addition of 100 nM estradiol. However, we failed to demonstrate any increase of TGF beta 1 mRNA after estradiol administration using Northern blot analysis. Further studies are needed to ascertain whether the estradiol-induced growth inhibition of PC3 cells is either mediated by other TGF beta species or exerted via alternative mechanism(s).
据报道，雌二醇对PC3人前列腺癌细胞的增殖活性有显著抑制作用，并伴有特定雌激素受体（ER）的实验证据。放射性配体结合分析显示PC3细胞核区室存在雌激素结合的高亲和力位点。此外，使用逆转录聚合酶链反应系统，我们获得了正常或变异ER mRNA的证据；后者缺少整个外显子4，与正常ER mRNA共表达，最近在我们实验室中得到了表征。还研究了雌二醇发挥的抑制作用是否可能由转化生长因子β（TGFβ）产量增加介导。使用抗TGFβ1单克隆抗体使PC3细胞的生长速率提高了3倍；这清楚地表明内源性TGFβ1水平很高。添加100 nM雌二醇后，这种作用几乎完全消失。然而，我们使用Northern印迹分析未能证明给予雌二醇后TGFβ1 mRNA有任何增加。需要进一步研究以确定雌二醇诱导的PC3细胞生长抑制是由其他TGFβ种类介导还是通过其他机制发挥作用。
