title: Differential gene expression in models of pituitary prolactin-producing tumoral cells.
abstract: Although several genes and signalling pathways have been identified as important effectors in the development of pituitary tumours, our understanding of pituitary tumorigenesis remains incomplete and is the focus of much current research. Use of the mRNA differential display technique in prolactinomas from D2-receptor knockout mice and in stable GH3 cell line clones with enhanced tumorigenicity in vivo has led to the identification of two genes that are involved in the pathogenic process--BMP-4 and RSUME. Bone morphogenetic protein-4 (BMP-4) has been found to have a crucial role in prolactinoma development and also in signalling crosstalk with oestrogens. In contrast, BMP-4 has an inhibitory role in corticotrophinomas. RSUME (RWD-containing sumoylation enhancer) was identified from a transformed lactosomatotrophic cell line that had increased tumorigenic and angiogenic potential. Expression of RSUME was induced under hypoxic conditions and it has a potential role during vascularization. The differential expression and action of BMP-4 in prolactinomas and corticotrophinomas highlights the importance of studying a gene with contrasting actions in two cell lineages of the same organ in order to understand the pituitary transformation process. Both BMP-4 and RSUME may be interesting targets for inhibiting steps involved in pituitary tumorigenesis.
authors.affiliation: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, FCEN, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Damiana
authors.initials: D
authors.lastname: Giacomini
authors.forename: Mariana
authors.initials: M
authors.lastname: Haedo
authors.forename: Juan
authors.initials: J
authors.lastname: Gerez
authors.forename: Jimena
authors.initials: J
authors.lastname: Druker
authors.forename: Marcelo
authors.initials: M
authors.lastname: Páez-Pereda
authors.forename: Marta
authors.initials: M
authors.lastname: Labeur
authors.forename: Gunter K
authors.initials: GK
authors.lastname: Stalla
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arzt
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis* / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D015175:Prolactinoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D009363:Neoplasm Proteins; C525338:RWDD3 protein, human; D017448:Receptors, Dopamine D2; D014157:Transcription Factors