title: Promyelocytic leukaemia (PML) protein expression in human placenta and choriocarcinoma.
abstract: Promyelocytic leukaemia (PML) protein, the product of the pml gene, is heterogeneously expressed in various normal and neoplastic tissues, and the fusion of the pml gene with retinoic acid receptor-alpha is believed to be a central mechanism in acute PML tumourigenesis. As PML is important for controlling major cellular processes, such as growth and differentiation, it is believed that it plays an important role during human gestation. The human placenta is a critical organ for the maintenance of gestation, but the expression pattern and functional significance of PML in the placenta have not been documented. The present study has therefore investigated the expression of PML in the human placenta and in choriocarcinoma, and has observed the biological effects following the overexpression of PML in choriocarcinoma cell lines (BeWo and JEG-3). In the human placenta, PML expression was readily found in villous stromal fibroblasts, capillary endothelial cells, Hofbauer cells, and occasionally in amnion cells. Moreover, immunoblotting of placental lysates demonstrated increased PML expression with increasing gestation. Interestingly, PML expression was confined to intermediate trophoblasts and syncytiotrophoblastic giant cells at the placental site (placental site giant cells) in the trophoblastic cell population. Intermediate trophoblasts at non-placental sites, and villous cytotrophoblasts and syncytiotrophoblasts consistently did not express PML. Further screening of PML expression in hydatidiform moles (n = 4) and choriocarcinomas (n = 7) also revealed selective PML expression in intermediate trophoblastic cells and syncytiotrophoblastic cells, but not in the cytotrophoblastic populations, which corresponds well with observations in the placental bed. Adenoviral transduction of PML resulted in a marked reduction in cell growth in both choriocarcinoma cell lines, which was associated with increased apoptosis. The findings of the present study strongly suggest that PML plays an important role in human placental development and growth, and in the pathobiology of trophoblasts and trophoblastic neoplasia.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. cjkim@plaza.snu.ac.kr
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Yoon
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Jun
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Park
authors.forename: So Young
authors.initials: SY
authors.lastname: Cho
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Yeon Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: Eun-Sil
authors.initials: ES
authors.lastname: Yu
mesh_terms: D002822:Choriocarcinoma / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014594:Uterine Neoplasms / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human