Volume 16, No 1, Jan 2006

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 16 Issue 1, January 2006: 93-98

ORIGINAL ARTICLES

Phosphorylated KDR can be located in the nucleus of neoplastic cells

Cristina Blazquez¹, Nathan Cook², Kingsley Micklem³, Adrian L Harris⁴, Kevin C Gatter², Francesco Pezzella²

¹Departamento de Bioquimica y Biologia Molecular I, Facultad de Biologia, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid 28040, Espania;²Cancer Research UK Tumour Pathology Group, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK;³Medical Informatics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK;⁴Cancer Research UK Molecular Oncology Laboratory, John Radcliffe Hospital, Oxford, OX3 9DU, UK Correspondence: Francesco Pezzella(francesco.pezzella@cancer.org.uk)

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.

Cell Research (2006) 16:93-98. doi:10.1038/sj.cr.7310012; published online 16 January 2006

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