Occurrence, regulation, and significance of progesterone receptors in human meningioma

The abundant expression of progesterone receptors (PR) in human meningiomas is well established. It is unknown, however, how PR expression is regulate d, especially since estrogen receptors (ER) are virtually absent in these t umors. At the mRNA level, ER splice variants occur in meningioma but these appear not to be involved in the apparently autonomous PR expression. In an earlier study. because other ER-inducible proteins were either not express ed at all (pS2) or were expressed at a very low level compared to their exp ression in breast cancer (Cathepsin-D), the authors have postulated that th e autonomous PR expression in meningioma is PR promoter-related rather than ER-related and have studied PR expression in cultured meningioma cells. PR levels appeared to decrease rapidly in vitro in monolayer as well as in th ree dimensional spheroid cultures. Culture conditions thus are not yet suff icient for the quantitative evaluation of PR expression. To evaluate whethe r PR deterioration is associated with cell turnover (meningiomas grow much faster in vitro than in vivo), the relationship between expression of the a poptotic proteins Bcl-2 and Pax and PR expression was investigated. Bcl-2 e xpression was found to be highest in meningioma with low PR levels, and in breast cancer tissue with high PR levels. Bax expression was not related to PR expression in any of the two tissues. Given the potential benefit of an tiprogestin treatment and the occurrence in meningiomas of a protein capabl e of binding to the estrogen-responsive element, the expression of PR in me ningioma remains a fascinating phenomenon which requires further investigat ion. (C) 2000 Elsevier Science Inc. All rights reserved.