Progesterone receptor isoform expression in human meningiomas

The majority of meningiomas express the progesterone receptor (PR), and the refore meningiomas are considered to be progesterone-responsive. In additio n, 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 differentia l expression of both isoforms is necessary to understand the effects of pro gesterone on meningioma growth. Therefore, in this study, PR-A and PR-B exp ression levels were determined in 61 human meningiomas by immunoblotting. T otal PR expression levels were determined with a li-and binding assay (LBA) (total PRLBA). 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 PRLBA levels (P <0.001). The PR-78 band intensity was negatively associated with that of PR-B (r(s)=-0.76, P <0.00 01). PR-78 may represent an endogenous degradation product, but a similar r egulation 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 th is variability may have some biological significance. Most meningiomas expr ess more PR-A than PR-B. Therefore in meningioma, assuming that PR-B is mor e transcriptionally active than PR-A, progesterone responsiveness could be based on transrepression rather than on transactivation. of target genes, a nd progesterone blockade may only be effective in certain subsets of mening iomas. (C) 2001 Elsevier Science Ltd. All rights reserved.