Position-dependent expression of GADD45alpha in rat brain tumours.
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.
Brú
Antonio
A
Department of Applied Mathematics, Faculty of Mathematics, Complutense University, Madrid, Spain.
del Fresno
Carlos
C
Soares-Schanoski
Alessandra
A
Albertos
Sonia
S
Brú
Isabel
I
Porres
Amelia
A
Rollán-Landeras
Eduardo
E
Dopazo
Ana
A
Casero
David
D
Gómez-Piña
Vanesa
V
García
Lourdes
L
Arnalich
Francisco
F
Alvarez
Rebeca
R
Rodríguez-Rojas
Alexandro
A
Fuentes-Prior
Pablo
P
López-Collazo
Eduardo
E
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
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; D012333:RNA, Messenger; C499073:Gadd45a protein, rat; D000097642:GADD45 Proteins