Identification of multiple differentially expressed messenger RNAs in normal and pathological trophoblast.
In an attempt to assess the molecular basis of phenotypic alterations present in the gestational trophoblastic diseases (GTDs) and to identify genes whose expression is specifically associated to these placental proliferative disorders we performed differential display techniques. Initially 19 candidate gene fragments were identified and differential expression was confirmed in eight of these fragments by Northern blot analysis. At the mRNA level ribosomal L26 (rL26), ribosomal L27 (rL27), a new Krüppel type zinc finger protein and TIS11d were preferentially expressed in normal early placenta (NEP) relative to complete hydatidiform mole (CHM), persistent gestational trophoblastic disease (PGTD) and choriocarcinoma JEG-3 cell line. In contrast, heterogeneous ribonucleoprotein A1 (hnRNPA1), the ferritin light chain mRNA, and the uncharacterized protein KIAA0992 were predominantly expressed in JEG-3 cell line. Finally, decorin, a prototype member of an expanding family of small leucine-rich proteoglycans, showed high expression in CHM. In addition we demonstrated by immunohistochemistry analysis that increased decorin mRNA in CHM reflected a genuine augmentation in average steady state mRNA levels within cells. Taken together, these findings provide several interesting candidates for regulation of tumorigenic expression as well as early placentation development, including those involved in protein synthesis (rL26 and rL27), metabolism (ferritin light chain), intercellular communication (decorin) and regulation of gene expression (Krüppel-like zinc finger, TIS11d and hnRNPA1). Information about such alterations in gene expression could be useful for elucidating the genetic events associated to gestational trophoblastic pathogenesis, developing new diagnostic markers, or determining novel therapeutic targets.
Durand
S
S
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Pabellón Argentina, Ala Oeste, Ciudad Universitaria, Argentina.
Abadie
P
P
Angeletti
S
S
Genti-Raimondi
S
S
D000328:Adult; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005260:Female; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005865:Gestational Age; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D009687:Nuclear Proteins; D011247:Pregnancy; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D051816:Tristetraprolin; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
C546878:DCN protein, human; D004268:DNA-Binding Proteins; D058575:Decorin; D016326:Extracellular Matrix Proteins; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C489216:RPL26 protein, human; D012269:Ribosomal Proteins; D051816:Tristetraprolin; C497552:ZFP36 protein, human; C000619656:hnRNPA1 protein, human; C034661:ribosomal proteins L27; C068804:ZBTB25 protein, human; D005293:Ferritins