Authors: Franck Gadal¹; Christophe Bozic²; Céline Pillot-Brochet²; Sophie Malinge²; Sarah Wagner²; Aurélie Le Cam²; Laurent Buffat²; Michel Crepin; François Iris³

Source: Nucleic Acids Research, Volume 31, Number 19, 01 October 2003 , pp. 5789-5804(16)

Publisher: Oxford University Press

Abstract:

To understand the cellular mechanisms of malignant transformation induced by constitutive activation of the ras oncogene (Ha-ras), we used a subtractive hybridization method (VGID™) together with an integrative analytical procedure based upon literature databases in the form of extensive interaction graphs. We found 166 over- and under-expressed genes which, in the human MCF7-ras breast epithelial cell line, are involved in the different aspects of tumoral transformation such as defined signaling pathways, cellular growth, protection against apoptosis, extracellular matrix and cytoskeleton remodeling. Integrative analysis led to the construction of a physiological model defining cross-talk and signaling pathway alterations which explicitly suggested mechanisms directly involved in tumor progression. The model further suggested points and means of intervention which could induce cell death in Ha-ras-transformed cells specifically. These hypotheses were directly tested in vitro and found to be largely correct, hence indicating that these new analytical and technological approaches allow the discovery of pathology-associated cellular mechanisms and physiologically defined targets leading to phenotype-specific pharmacological interventions.

Document Type: Research article

DOI: http://dx.doi.org/10.1093/nar/gkg762

Affiliations: 1: *To whom correspondence should be addressed. Tel fgadal@club-internet.fr, Fax: +33 1 48 38 77 20 2: Valigen, Tour Neptune, 92086 Paris La Défense, France and 3: Ecole Centrale de Paris, Grande voie des vignes, 92295 Chatenay Malabry, France

Publication date: 2003-10-01

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• Nucleic Acids Research (NAR) is a fully Open Access journal, providing rapid publication of leading edge research into the nucleic acids under the following categories: chemistry, computational biology, genomics, molecular biology, nucleic acid enzymes, RNA and structural biology. There is a Survey and Summary section, and methods papers are published
  in NAR Methods Online. Each year the first issue is devoted to biological databases, and a later issue to relevant web-based software resources.

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