1. ¹Departamento de Bioquimica y Biologia Molecular I, Facultad de Biologia, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid 28040, Espania
2. ²Cancer Research UK Tumour Pathology Group, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK
3. ³Medical Informatics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK
4. Cancer Research UK Molecular Oncology Laboratory, John Radcliffe Hospital, Oxford, OX3 9DU, UK

Received 25 May 2005; Revised 14 October 2005; Accepted 22 October 2005.

Abstract

KDR (kinase insert domain receptor) phosphorylation induces several effects which lead eventually to cell proliferation and survival. The precise mechanisms by which KDR, once it is activated, communicates with the nucleus are starting to be understood but have not yet been completely unravelled. Two in vitro studies on animal cell lines reported in the literature have demonstrated that, following stimulation with VEGF, KDR is actually translocated within the nucleus. Our aim was to investigate whether this translocation occurs in human cells both in vitro and in vivo. Using laser scanning confocal microscopy, a variable nuclear localization of phosphorylated and total KDR in cell lines and tumour samples was found. In human neoplastic cell lines, hypoxic stimulation greatly increased the nuclear amount of total KDR but less so that of the phosphorylated form. Only after hypoxia and VEGF stimulation there was a comparably increased expression of phosphorylated and total KDR observed in the nuclei of these cells. We conclude that neoplastic cells show a variable expression of total and phosphorylated KDR in the nucleus. The precise functional meaning of nuclear location remains to be established.