Position-dependent expression of GADD45α in rat brain tumours

Antonio Brú, Carlos del Fresno, Alessandra Soares-Schanoski, Sonia Albertos, Isabel Brú, Amelia Porres, Eduardo Rollán-Landeras, Ana Dopazo, David Casero, Vanesa Gómez-Piña, Lourdes García, Francisco Arnalich, Rebeca Alvarez, Alexandro Rodríguez-Rojas, Pablo Fuentes-Prior, Eduardo López-Collazo

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.