Position-dependent expression of GADD45α in rat brain tumours
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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, GADD45α, was expressed at much lower levels in the peripheral zone, as compared to tumour core samples. These differences in GADD45α mRNA transcription levels have been confirmed by quantitative analysis via real time PCR, and protein levels of GADD45α also exhibit the same pattern of differential expression. Our findings suggest that GADD45α might play a major role in the regulation of brain tumour invasive potential.
KeywordsTumour growth GADD45α p21
Growth arrest and DNA-damage-inducible gene 45α
This work is dedicated to the memory of our colleague and friend Dr. Lourdes Gómez-García. We thank Dr. Marta Izquierdo for animal handling. This study was supported by grants from ‘Fundación Médica Mutua Madrileña Automovilística’ to E. López-Collazo and A. Brú and by Acción Especial AE5/06-14364 from Universidad Complutense and partially supported by European Contract MRTN-CT-2004-503661 to A. Brú.
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