Koehorst S G, Spapens M E, Van Der Kallen C J, Van 'T Verlaat J W, Blaauw G, Thijssen J H, Blankenstein M A
Department of Endocrinology, University Hospital Utrecht, The Netherlands.
Int J Biol Markers. 1998 Jan-Mar;13(1):16-23. doi: 10.1177/172460089801300104.
Autonomous expression of progesterone receptors (PR) in human meningiomas is well established. To evaluate whether, similar to progesterone receptors, other estrogen-inducible proteins are also autonomously expressed in meningiomas, concentrations of pS2 and cathepsin-D (Cath-D) were measured in 52 meningiomas. No pS2 protein was detectable in 52/52 tested meningiomas. The Cath-D protein was measurable in all 52 meningiomas, but the mean concentration of Cath-D in meningioma cytosols was 2.4-fold lower than that of a group of 54 breast tumors (p < 0.001). These results indicate that autonomous expression is a PR-related rather than an estrogen receptor-related phenomenon and, consequently, that estradiol is probably not responsible for PR synthesis in human meningiomas. To evaluate the role of other, non-estradiol-dependent signalling pathways in PR synthesis, the effects of EGF, Forskolin and phorbol ester on PR synthesis were tested in vitro. No PR was detectable after the addition of EGF to six different primary cultures. Forskolin and TPA addition caused a morphological change in meningioma cells, but did not induce PR or pS2 synthesis in two different primary meningioma cultures. We conclude that PR synthesis in human meningiomas cannot be triggered by switching on the signalling pathways activated by these growth factors.
人类脑膜瘤中孕激素受体(PR)的自主表达已得到充分证实。为评估是否与孕激素受体类似,其他雌激素诱导蛋白在脑膜瘤中也自主表达,我们检测了52例脑膜瘤中pS2和组织蛋白酶D(Cath-D)的浓度。在52例检测的脑膜瘤中均未检测到pS2蛋白。所有52例脑膜瘤中均可检测到Cath-D蛋白,但脑膜瘤细胞溶质中Cath-D的平均浓度比54例乳腺肿瘤组低2.4倍(p<0.001)。这些结果表明自主表达是一种与PR相关而非与雌激素受体相关的现象,因此,雌二醇可能不是人类脑膜瘤中PR合成的原因。为评估其他非雌二醇依赖性信号通路在PR合成中的作用,我们在体外测试了表皮生长因子(EGF)、福斯高林和佛波酯对PR合成的影响。向六种不同的原代培养物中添加EGF后未检测到PR。添加福斯高林和佛波酯可导致脑膜瘤细胞形态改变,但在两种不同的原代脑膜瘤培养物中未诱导PR或pS2合成。我们得出结论,人类脑膜瘤中的PR合成不能通过开启这些生长因子激活的信号通路来触发。