Differential gene expression in models of pituitary prolactin-producing tumoral cells.
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.
Giacomini
Damiana
D
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, FCEN, Universidad de Buenos Aires, Buenos Aires, Argentina.
Haedo
Mariana
M
Gerez
Juan
J
Druker
Jimena
J
Páez-Pereda
Marcelo
M
Labeur
Marta
M
Stalla
Gunter K
GK
Arzt
Eduardo
E
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
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D009363:Neoplasm Proteins; C525338:RWDD3 protein, human; D017448:Receptors, Dopamine D2; D014157:Transcription Factors