Progesterone Receptor Synthesis in Human Meningiomas: Relation to the Estrogen-Induced Proteins pS2 and Cathepsin-D and Influence of Epidermal Growth Factor,Forskolin and Phorbol Ester in vitro
Restricted accessResearch articleFirst published online January, 1998
Progesterone Receptor Synthesis in Human Meningiomas: Relation to the Estrogen-Induced Proteins pS2 and Cathepsin-D and Influence of Epidermal Growth Factor,Forskolin and Phorbol Ester in vitro
Autonomous expression of progesterone receptors (PR) in human meningiomas is well established. To evaluate whether, similar to progesterone receptors, other estrogen-inducible proteins are also autonomously expressed in meningiomas, concentrations of pS2 and cathepsin-D (Cath-D) were measured in 52 meningiomas. No pS2 protein was detectable in 52/52 tested meningiomas. The Cath-D protein was measurable in all 52 meningiomas, but the mean concentration of Cath-D in meningioma cytosols was 2.4-fold lower than that of a group of 54 breast tumors (p < 0.001). These results indicate that autonomous expression is a PR-related rather than an estrogen receptor-related phenomenon and, consequently, that estradiol is probably not responsible for PR synthesis in human meningiomas. To evaluate the role of other, non-estradiol-dependent signalling pathways in PR synthesis, the effects of EGF, Forskolin and phorbol ester on PR synthesis were tested in vitro. No PR was detectable after the addition of EGF to six different primary cultures. Forskolin and TPA addition caused a morphological change in meningioma cells, but did not induce PR or pS2 synthesis in two different primary meningioma cultures. We conclude that PR synthesis in human meningiomas cannot be triggered by switching on the signalling pathways activated by these growth factors.
BlaauwG., BlankensteinM.A., LambertsS.W.J.Sex steroid receptors in human meningiomas.Acta Neurochir1986; 79: 42–6.
2.
BlankensteinM.A., BlaauwG., LambertsS.W.J., MulderE.Presence of progesterone receptors and absence of estrogen receptors in human intracranial meningioma cytosols.Eur J Cancer Clin Oncol1983; 19: 365–70.
3.
BlankensteinM.A., van der Meulen-DijkC., ThijssenJ.H.H.Assay of estrogen and progestin receptors in human meningioma cytosols using immunological methods.Clin Chim Acta1987; 165: 189–95.
4.
BlankensteinM.A., BernsP.M., BlaauwG., MulderE., ThijssenJ.H.H.Search for the estrogen receptor in human meningioma tissue sections with a monoclonal antibody against the human estrogen receptor.Cancer Res1986; 46: 4268s–70s.
MaxwellM., GalanopolosT., Neville-GoldenJ., AntoniadesH.N.Expression of androgen and progesterone receptors in primary human meningiomas.J Neurosurg1993; 78: 456–62.
7.
KoehorstS.G.A., JacobsH.M., TilanusM.G.J., BouwensA.G.M., ThijssenJ.H.H., BlankensteinM.A.Aberrant estrogen receptor species in human meningioma tissue.J Steroid Biochem Molec Biol1992; 43: 57–61.
8.
KoehorstS.G.A., JacobsH.M., ThijssenJ.H.H., BlankensteinM.A.Wild type and alternatively spliced estrogen receptor messenger RNA in human meningioma tissue and MCF7 breast cancer cells.J Steroid Biochem Molec Biol1993; 45: 227–33.
9.
FuquaS.A.W., FitzgeraldS.D., AllredD.C.. Inhibition of estrogen receptor action by a naturally occurring variant in human breast tumors.Cancer Res1992; 52: 483–6.
10.
KoehorstS.G.A., CoxJ.J., DonkerG.H., Lopes da SilvaS., BurbachJ.P.H., ThijssenJ.H.H., BlankensteinM.A.Functional analysis of an alternatively spliced estrogen receptor lacking exon 4 isolated from MCF7 breast cancer cells and meningioma tissue.Mol Cell Endocrinol1994; 101: 237–45.
11.
KoehorstS.G.A., JacobsH.M., ThijssenJ.H.H., BlankensteinM.A.Detection of an estrogen receptor-like protein in human meningiomas by band shift assay using a synthetic estrogen responsive element.Br J Cancer1993; 68: 290–4.
12.
ScottG.K., KastnerP., VigneJ., BenzC.C.Truncated forms of DNA-binding oestrogen receptors in human breast cancer.J Clin Invest1991; 88: 700–6.
13.
BrownA.M.C., JeltschJ.M., RobertsM., ChambonP.Activation of the pS2 gene is a primary response to estrogen in the human breast cancer cell line MCF7.Proc Natl Acad Sci USA1984; 81: 6344–8.
14.
CavaillesV., AugereauP., GarciaM.. Estrogens and growth factors induce the mRNA of the 52K-pro-cathepsin-D secreted by breast cancer cells.Nucl Acid Res1988; 16: 1903–19.
15.
KoperJ.W., FoekensJ.A., LambertsS.W.J.Effect of progesterone on the response to epidermal growth factor and other growth factors in cultured human meningioma cells.Cancer Res1990; 50: 2604–7.
16.
AronicaS.M., KatzenellenbogenB.S.Progesterone receptor regulation in uterine cells: Stimulation by estrogen, cyclic adenosine 3’, 5’-monophosphate, and insulin-like growth factor I and suppression by antiestrogens and protein kinase inhibitors.Endocrinology1991; 128: 2045–53.
17.
SumidaC., PasqualiniJ.R.Stimulation of progesterone receptor by phorbol ester and cyclic AMP in fetal uterine cells.Mol Cell Endocrinol1990; 69: 207–15.
18.
CavaillesV., GarciaM., RochefortH.Regulation of cathepsin-D and pS2 gene expression by growth factors in MCF7 human breast cancer cells.Mol Endocrinol1989; 3: 552–8.
19.
BradfordM.M.A rapid and sensitive method for the quantitation of protein using the principle of protein dyebinding.Anal Biochem1976; 72: 248–55.
20.
NunezA.M., JakowlevS., BriandJ.P.. Characterization of the estrogen-induced pS2 protein secreted by the human breast cancer cell line MCF7.Endocrinology1987; 121: 1759–65.
21.
RioM.C., BellocqJ.P., DanielJ.Y.. Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa.Science1988; 241: 705–8.
22.
RioM.C., BellocqJ.P., GairardB.. Specific expression of the pS2 gene in subclasses of breast cancer - comparison with expression of the progesterone receptors and the oncogene ERRB2.Proc Natl Acad Sci USA1987; 84: 9243–7.
23.
AugerauP., GarciaM., MatteiM.G.. Cloning and sequencing of the 52K cathepsin D complementary deoxyribonucleic acid of MCF7 breast cancer cells and mapping of chromosome 11.Mol Endocrinol1988; 2: 186–92.
24.
CaponyF., MorissetM., BarrettA.J.. Phosphorylation, glycosylation and proteolytic activity of the 52K estrogen-induced protein secreted by MCF7 cells.J Cell Biol1987; 104: 253–62.
25.
WestleyB., RochefortH.A secreted glycoprotein induced by estrogen in human breast cancer cell lines.Cell1980; 20: 352–2.
26.
VignonF., CaponyF., ChambonM.. Autocrine growth stimulation of the MCF7 breast cancer cells by the estrogen-regulated 52K protein.Endocrinology1986; 118: 1537–45.
27.
BriozzoP., MorissetM., CaponyF.. In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells.Cancer Res1988; 48: 3688–92.
28.
RochefortH., CaponyF., GarciaM.. Estrogen-induced lysosomal proteases secreted by breast cancer cells.A role in carcinogenesis? J Cell Biochem1987; 35: 17–29.
29.
FoekensJ.A., RioM.C., SeguinP.. Prediction of relapse and survival in breast cancer patients by pS2 status.Cancer Res1990; 50: 3832–7.
30.
BouillotP., PellissierJ-F, DevictorB.. Quantitative imaging of estrogen-regulated protein, and growth fraction: immunocytochemical assays in 52 meningiomas.J Neurosurg1994; 81: 765–73.
31.
SivaparvathiM., McCutcheonI., SawayaR., NicholsonG.L., RaoJ.S.Expression of cysteine protease inhibitors in human gliomas en meningiomas.Clin Exp Metastasis1996; 14: 344–50.
32.
BlankensteinM.A., van der Meulen-DijkC., ThijssenJ.H.H.Effect of steroids and antisteroids on human meningioma cells in primary culture.J Steroid Biochem1989; 34: 419–21.
