The truncated estrogen receptor alpha variant lacking exon 5 is not involved in progesterone receptor expression in meningiomas

Abstract

Human meningioma tissues are mostly estrogen receptor (ER) negative and progesterone receptor (PR) positive in ligand binding and enzyme immuno assays. To explain this apparently ER independent PR expression, we investigated the existence of a ‘hidden’ ER variant, which would be capable of activating transcription of the PR gene. Total RNA of seven meningiomas, two breast cancer tissues and of MCF7 cells was analyzed by RT-PCR using primers situated in exon 4 and exon 6. Differential hybridization of the PCR transcripts with probes in exon 4 and 5 respectively, revealed a wild type ER (wtER) fragment and an exon 5 deleted ER variant (ERΔ5). PCR products of two meningiomas were cloned for sequence analysis. The result confirmed the existence of a wtER and ERΔ5. RT-PCR followed by Southern analysis was performed on mRNA of 23 meningiomas to determine the amount of ERΔ5 relative to wtER, which was compared to the PR content of the tissues. In contrast to our initial hypothesis and literature data on breast cancer, there was no relationship between the ERΔ5/wtER ratio and PR protein concentration. It is therefore concluded that ERΔ5 mRNA does not play the dominant role in PR synthesis in meningioma tissue.