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RNA interference against Hec1 inhibits tumor growth in vivo

Gene Therapy volume 13, pages 1–7 (2006)Cite this article

Abstract

Hec1 (highly expressed in cancer) plays an important role in chromosome segregation by interacting with a subset of checkpoint proteins that survey proper chromosome alignment and bipolar spindle attachment. In order to disrupt mitotic progression of tumor cell lines, we have used retrovirus and adenovirus vectors that inhibit Hec1 synthesis. Vector-expressed short hairpin RNAs (shRNAs) caused very efficient depletion of the target protein, cellular arrest and considerable mitotic catastrophe induction 96 h post infection in human cervix-adenocarcinoma (HeLa) and glioblastoma (U-373-MG) cell lines. Furthermore, adenocarcinomas induced in the flanks of nude mice show significant reduction in size compared with control when treated with either Hec1-shRNA retroviruses or adenoviruses. These results indicate that depletion of Hec1 could be used as a new strategy to block the dividing cell, and therefore against cancer.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

RNAi:

RNA interference

dsRNA:

double-stranded RNA

shRNAs:

short hairpin RNAs

RISC:

RNA-induced silencing complex

Hec1:

highly expressed in cancer

pRiHec1:

retroviral plasmid carrying the DNA corresponding to Hec1-shRNA.

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Acknowledgements

We are indebted to Dr John Kilmartin (MRC Laboratory of Molecular Biology, Cambridge, UK) for providing anti-Hec1 antibody several times. This study was supported by a grant from the Comunidad de Madrid 08.1/0039.1/2003 and from the Ministerio de Ciencia y Tecnología SAF 2002-01100. The Centro de Biología Molecular S.O. is also the recipient of an institutional grant from the Ramón Areces Foundation. EN Gurzov was supported by a grant from the Fundación Carolina-Ministerio de Asuntos Exteriores de España.

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Authors and Affiliations

  1. Department of Molecular Biology, Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, Madrid, Spain

    E N Gurzov & M Izquierdo

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  1. E N Gurzov
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  2. M Izquierdo
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Correspondence to M Izquierdo.

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Gurzov, E., Izquierdo, M. RNA interference against Hec1 inhibits tumor growth in vivo. Gene Ther 13, 1–7 (2006). https://doi.org/10.1038/sj.gt.3302595

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