Original Article

Gene Therapy (2006) 13, 1–7. doi:10.1038/sj.gt.3302595; published online 25 August 2005

RNA interference against Hec1 inhibits tumor growth in vivo

E N Gurzov1 and M Izquierdo1

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

Correspondence: Dr M Izquierdo, Department of Molecular Biology, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco 28049 Madrid, Spain. E-mail: mizquierdo@cbm.uam.es

Received 13 April 2005; Revised 2 June 2005; Accepted 22 June 2005; Published online 25 August 2005.

Top

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.

Keywords:

RNA interference, Hec1, glioma, HeLa cells

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.

Top

MORE ARTICLES LIKE THIS

Extra navigation

.

naturejobs

natureproducts


ADVERTISEMENT