title: Position-dependent expression of GADD45alpha in rat brain tumours.
abstract: Although the complex and multifactorial process of tumour growth has been extensively studied for decades, our understanding of the fundamental relationship between tumour growth dynamics and genetic expression profile remains incomplete. Recent studies of tumour dynamics indicate that gene expression in solid tumours would depend on the distance from the centre of the tumour. Since tumour proliferative activity is mainly localised to its external zone, and taking into account that generation and expansion of genetic mutations depend on the number of cell divisions, important differences in gene expression between central and peripheral sections of the same tumour are to be expected. Here, we have studied variations in the genetic expression profile between peripheral and internal samples of the same brain tumour. We have carried out microarray analysis of mRNA expression, and found a differential profile of genetic expression between the two cell subsets. In particular, one major nuclear protein that regulates cell responses to DNA-damaging and stress signals, GADD45alpha, was expressed at much lower levels in the peripheral zone, as compared to tumour core samples. These differences in GADD45alpha mRNA transcription levels have been confirmed by quantitative analysis via real time PCR, and protein levels of GADD45alpha also exhibit the same pattern of differential expression. Our findings suggest that GADD45alpha might play a major role in the regulation of brain tumour invasive potential.
authors.affiliation: Department of Applied Mathematics, Faculty of Mathematics, Complutense University, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Brú
authors.forename: Carlos
authors.initials: C
authors.lastname: del Fresno
authors.forename: Alessandra
authors.initials: A
authors.lastname: Soares-Schanoski
authors.forename: Sonia
authors.initials: S
authors.lastname: Albertos
authors.forename: Isabel
authors.initials: I
authors.lastname: Brú
authors.forename: Amelia
authors.initials: A
authors.lastname: Porres
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rollán-Landeras
authors.forename: Ana
authors.initials: A
authors.lastname: Dopazo
authors.forename: David
authors.initials: D
authors.lastname: Casero
authors.forename: Vanesa
authors.initials: V
authors.lastname: Gómez-Piña
authors.forename: Lourdes
authors.initials: L
authors.lastname: García
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich
authors.forename: Rebeca
authors.initials: R
authors.lastname: Alvarez
authors.forename: Alexandro
authors.initials: A
authors.lastname: Rodríguez-Rojas
authors.forename: Pablo
authors.initials: P
authors.lastname: Fuentes-Prior
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D008279:Magnetic Resonance Imaging; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; D012333:RNA, Messenger; C499073:Gadd45a protein, rat; D000097642:GADD45 Proteins