Progesterone receptor isoform expression in human meningiomas.
The majority of meningiomas express the progesterone receptor (PR), and therefore meningiomas are considered to be progesterone-responsive. In addition, an association has been reported between PR and prognosis. At least two PR isoforms exist, PR-B (116--120 kDa) and PR-A (81 kDa), each of which are likely to have different biological functions. Knowledge of the differential expression of both isoforms is necessary to understand the effects of progesterone on meningioma growth. Therefore, in this study, PR-A and PR-B expression levels were determined in 61 human meningiomas by immunoblotting. Total PR expression levels were determined with a ligand binding assay (LBA) (total PR(LBA)). Both PR isoforms and an additional PR 78 kDa protein (PR-78) were expressed in the meningiomas. Meningiomas expressing more PR-A than PR-B had significantly higher total PR(LBA) levels (P<0.001). The PR-78 band intensity was negatively associated with that of PR-B (r(s)=-0.76, P<0.0001). PR-78 may represent an endogenous degradation product, but a similar regulation pathway in the biogenesis of both PR-B and PR-78 is not excluded. Meningiomas contain both PR isoforms, but in highly variable ratios and this variability may have some biological significance. Most meningiomas express more PR-A than PR-B. Therefore in meningioma, assuming that PR-B is more transcriptionally active than PR-A, progesterone responsiveness could be based on transrepression rather than on transactivation of target genes, and progesterone blockade may only be effective in certain subsets of meningiomas.
Verheijen
F M
FM
Department of Endocrinology, University Medical Center Utrecht, KE 03-139.2, PO Box 85090, NL-3508 AB Utrecht, The Netherlands. f.m.verheijen@lab.azu.nl
Sprong
M
M
Jacobs
H M
HM
Donker
G H
GH
Amelink
G J
GJ
Thijssen
J H
JH
Blankenstein
M A
MA
D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism*; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
D008024:Ligands; D020033:Protein Isoforms; D011980:Receptors, Progesterone