Wild type and alternatively spliced estrogen receptor messenger RNA in human meningioma tissue and MCF7 breast cancer cells.
Human meningiomas are rich in progesterone receptors (PR), which appear to be expressed autonomously. To investigate whether estrogen receptor (ER) variants which do not bind the ligand, but may constitutively induce PR expression, prevail in meningioma, we amplified cDNA by PCR in order to detect mRNA coding for the ER in meningioma which were ER-negative/PR-positive at the protein level. We screened for a portion of the ER which includes the DNA binding domain, the hinge region and the ligand binding domain. For this part of the ER we found a wild type mRNA in all 8 meningiomas tested. No mutations were detected. Apart from this transcript we found two alternatively spliced products missing exons 4 and 7, respectively in 8/8 meningioma specimens. These two products were not exclusive for meningioma, since they were also detected in the MCF7 breast cancer cell line which was used as control. ER deletion mutants missing exon 7 have already been reported [Ref. 1; Molec. Endocr. 5 (1991) 1571-1577]. These are dominant negative. To our knowledge, this is the first report on ER mutants missing exon 4. The presence of ER variants missing exon 4, which is probably not able to bind heat shock protein 90 and therefore may be constitutively active, might explain the autonomous expression of PR in meningioma.
Department of Endocrinology, Academic Hospital Utrecht, The Netherlands.
S G
SG
Koehorst
H M
HM
Jacobs
J H
JH
Thijssen
M A
MA
Blankenstein
D017398:Alternative Splicing; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D006801:Humans; D008579:Meningioma / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D004247:DNA