Original Paper

Medical Oncology

, Volume 24, Issue 4, pp 436-444

Position-dependent expression of GADD45α in rat brain tumours

  • Antonio BrúAffiliated withDepartment of Applied Mathematics, Faculty of Mathematics, Complutense University
  • , Carlos del FresnoAffiliated withResearch Unit, Fundación para la Investigación Hospital La Paz
  • , Alessandra Soares-SchanoskiAffiliated withResearch Unit, Fundación para la Investigación Hospital La Paz
  • , Sonia AlbertosAffiliated withGastroenterology Unit, Instituto Nacional de Salud Carlos III, Hospital Carlos III
  • , Isabel BrúAffiliated withCentro de Salud La Estación
  • , Amelia PorresAffiliated withClinical Biochemistry Unit, Fundación Jímenez Díaz
  • , Eduardo Rollán-LanderasAffiliated withFaculty of Veterinary, Complutense University
  • , Ana DopazoAffiliated withNational Center of Cardiovascular Research
  • , David CaseroAffiliated withDepartment of Applied Mathematics, Faculty of Mathematics, Complutense University
    • , Vanesa Gómez-PiñaAffiliated withResearch Unit, Fundación para la Investigación Hospital La Paz
    • , Lourdes GarcíaAffiliated withResearch Unit, Fundación para la Investigación Hospital La Paz
    • , Francisco ArnalichAffiliated withResearch Unit, La Paz Hospital
    • , Rebeca AlvarezAffiliated withNational Center of Cardiovascular Research
    • , Alexandro Rodríguez-RojasAffiliated withResearch Unit, Fundación para la Investigación Hospital La Paz
    • , Pablo Fuentes-PriorAffiliated withCardiovascular Research Center, CSIC-ICCC
    • , Eduardo López-CollazoAffiliated withResearch Unit, Fundación para la Investigación Hospital La Paz Email author 

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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, 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.

Keywords

Tumour growth GADD45α p21