Progesterone Receptor Synthesis in Human Meningiomas: Relation to the Estrogen-Induced Proteins pS2 and Cathepsin-D and Influence of Epidermal Growth Factor, Forskolin and Phorbol Ester in vitro

Author:

Koehorst S.G.A.1,Spapens M.E.D.1,Van Der Kallen C.J.H.1,Van'T Verlaat J.W.2,Blaauw G.3,Thijssen J.H.H.1,Blankenstein M.A.1

Affiliation:

1. Department of Endocrinology, University Hospital Utrecht, Utrecht

2. Department of Neurosurgery, University Hospital Utrecht, Utrecht

3. Department of Neurosurgery, De Wever Hospital, Heerlen - The Netherlands

Abstract

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.

Publisher

SAGE Publications

Subject

Cancer Research,Clinical Biochemistry,Oncology,Pathology and Forensic Medicine

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