Titre
Differentiation-dependent expression of the BCL-2 proto-oncogene in the human trophoblast lineage.
Type
article
Institution
Externe
Périodique
Journal of the Society For Gynecologic Investigation
Auteur(s)
Sakuragi, N.
Auteure/Auteur
Matsuo, H.
Auteure/Auteur
Coukos, G.
Auteure/Auteur
Furth, E.E.
Auteure/Auteur
Bronner, M.P.
Auteure/Auteur
VanArsdale, C.M.
Auteure/Auteur
Krajewsky, S.
Auteure/Auteur
Reed, J.C.
Auteure/Auteur
Strauss, J.F.
Auteure/Auteur
Liens vers les personnes
ISSN
1071-5576
Statut éditorial
Publié
Date de publication
1994
Volume
1
Numéro
2
Première page
164
Dernière page/numéro d’article
172
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Résumé
OBJECTIVE: We explored the role of the BCL-2 proto-oncogene in the life cycle of trophoblast cells by examining: 1) the patterns of BCL-2 expression in normal placenta at various gestational ages and in specimens of hydatidiform moles and choriocarcinomas, and 2) the effects of cyclic adenosine monophosphate (cAMP) treatment of JEG-3 choriocarcinoma cells, which induces differentiated functions, on BCL-2.
METHODS: BCL-2 protein was localized by indirect immunofluorescence and immunoperoxidase staining of tissue sections and cells using monoclonal and polyclonal antibodies. Western and Northern blotting were used to assess BCL-2 and p53 protein and mRNA levels, respectively. JEG-3 cells were transfected with a BCL-2 expression plasmid to establish that BCL-2 protein could be expressed at high levels in this cell type.
RESULTS: BCL-2 immunostaining was most prominent in the syncytiotrophoblast of normal placenta. It was found in syncytiotrophoblast of complete and partial hydatidiform moles, whereas cytotrophoblast staining was weak. BCL-2 immunostaining was also barely detectable in choriocarcinoma cells (JEG-3 cells) and a primary choriocarcinoma. However, BCL-2 protein could be transiently overexpressed in JEG-3 cells by transfection with an expression plasmid. Western blot analysis revealed low levels of BCL-2 in JEG-3 cells and a rise in BCL-2 protein in placental extracts from 10 weeks' gestation to term. In contrast, p53 protein was abundant in JEG-3 cells and normal placenta at 10 weeks' gestation, but low at term, BCL-2 transcripts were substantially more abundant in term placenta than in JEG-3 cells. Treatment of JEG-3 cells with 8-Br-cAMP, which induces genes characteristic of the syncytiotrophoblast, raised BCL-2 protein approximately twofold, whereas p53 mRNA declined.
CONCLUSIONS: We conclude that: 1) There is a differentiation-dependent pattern of BCL-2 expression in the placenta, with the protein being most abundant in terminally differentiated trophoblast cells; 2) there appears to be an inverse relation between BCL-2 and p53 expression in trophoblast; and 3) cAMP regulates BCL-2 protein in trophoblast cells. We speculate that the expression of BCL-2 in terminally differentiated trophoblast cells, and hence resistance to apoptotic cell death, may be one mechanism by which trophoblast mass is preserved during pregnancy. Conversely, the relatively low expression of BCL-2 in choriocarcinoma cells may render them more susceptible to apoptosis.
METHODS: BCL-2 protein was localized by indirect immunofluorescence and immunoperoxidase staining of tissue sections and cells using monoclonal and polyclonal antibodies. Western and Northern blotting were used to assess BCL-2 and p53 protein and mRNA levels, respectively. JEG-3 cells were transfected with a BCL-2 expression plasmid to establish that BCL-2 protein could be expressed at high levels in this cell type.
RESULTS: BCL-2 immunostaining was most prominent in the syncytiotrophoblast of normal placenta. It was found in syncytiotrophoblast of complete and partial hydatidiform moles, whereas cytotrophoblast staining was weak. BCL-2 immunostaining was also barely detectable in choriocarcinoma cells (JEG-3 cells) and a primary choriocarcinoma. However, BCL-2 protein could be transiently overexpressed in JEG-3 cells by transfection with an expression plasmid. Western blot analysis revealed low levels of BCL-2 in JEG-3 cells and a rise in BCL-2 protein in placental extracts from 10 weeks' gestation to term. In contrast, p53 protein was abundant in JEG-3 cells and normal placenta at 10 weeks' gestation, but low at term, BCL-2 transcripts were substantially more abundant in term placenta than in JEG-3 cells. Treatment of JEG-3 cells with 8-Br-cAMP, which induces genes characteristic of the syncytiotrophoblast, raised BCL-2 protein approximately twofold, whereas p53 mRNA declined.
CONCLUSIONS: We conclude that: 1) There is a differentiation-dependent pattern of BCL-2 expression in the placenta, with the protein being most abundant in terminally differentiated trophoblast cells; 2) there appears to be an inverse relation between BCL-2 and p53 expression in trophoblast; and 3) cAMP regulates BCL-2 protein in trophoblast cells. We speculate that the expression of BCL-2 in terminally differentiated trophoblast cells, and hence resistance to apoptotic cell death, may be one mechanism by which trophoblast mass is preserved during pregnancy. Conversely, the relatively low expression of BCL-2 in choriocarcinoma cells may render them more susceptible to apoptosis.
Sujets
PID Serval
serval:BIB_B14A698DFDE1
PMID
Date de création
2014-10-14T10:43:28.538Z
Date de création dans IRIS
2025-05-21T03:20:08Z