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  • Oncogenomics
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Transfer of chromosome 3 fragments suppresses tumorigenicity of an ovarian cancer cell line monoallelic for chromosome 3p

Oncogene volume 26, pages 618–632 (2007)Cite this article

Abstract

Multiple chromosome 3p tumor suppressor genes (TSG) have been proposed in the pathogenesis of ovarian cancer based on complex patterns of 3p loss. To attain functional evidence in support of TSGs and identify candidate regions, we applied a chromosome transfer method involving cell fusions of the tumorigenic OV90 human ovarian cancer cell line, monoallelic for 3p and an irradiated mouse cell line containing a human chromosome 3 in order to derive OV90 hybrids containing normal 3p fragments. The resulting hybrids showed complete or incomplete suppression of tumorigenicity in nude mouse xenograft assays, and varied in their ability to form colonies in soft agarose and three-dimensional spheroids in a manner consistent with alteration of their in vivo tumorigenic phenotypes. Expression microarray analysis identified a set of common differentially expressed genes, such as SPARC, DAB2 and VEGF, some of which have been shown implicated in ovarian cancer. Genotyping assays revealed that they harbored normal 3p fragments, some of which overlapped candidate TSG regions (3p25–p26, 3p24 and 3p14-pcen) identified previously in loss of heterozygosity analyses of ovarian cancers. However, only the 3p12-pcen region was acquired in common by all hybrids where expression microarray analysis identified differentially expressed genes. The correlation of 3p12-pcen transfer and tumor suppression with a concerted re-programming of the cellular transcriptome suggest that the putative TSG may have affected key underlying events in ovarian cancer.

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Acknowledgements

We thank Suzanna Arcand, Henriette Gourdeau, Lise Portelance, Manon de Ladurantaye, Marise Roy, Philippe O. Gannon and Jean-Simon Diallo for technical assistance and helpful discussions. NALC is the recipient of a studentship from the Research Institute of the McGill University Health Centre. VO is a recipient of studentships from the Canadian Institutes of Health Research (CIHR) and Canderel fund of the Institut du Cancer de Montréal. ENM is a recipient of a studentship from the Natural Sciences and Engineering Research Council of Canada (NSERC), CIHR and the Fonds de Recherche en Santé du Québec (FRSQ). A-MM-M is a recipient of Chercheur National fellowship from the FRSQ. DMP is a Clinicien-Chercheur Senior from the FRSQ. This research was supported by a grant from the CIHR to PNT, A-M M-M, MC and DMP.

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Authors and Affiliations

  1. Department of Human Genetics, McGill University, Montréal, Canada

    N A L Cody, E N Manderson, M C J Quinn & P N Tonin

  2. Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Institut du cancer de Montréal, Montréal, Canada

    V Ouellet, A Filali-Mouhim, M Zietarska, D M Provencher & A-M Mes-Masson

  3. The Research Institute of the McGill University Health Centre, Montréal, Canada

    P Tellis, M Chevrette & P N Tonin

  4. Division de gynécologie oncologique, Université de Montréal, Montréal, Canada

    D M Provencher

  5. Département de médicine, Université de Montréal, Montréal, Canada

    A-M Mes-Masson

  6. Department of Surgery, Urology Division, McGill University, Montréal, Canada

    M Chevrette

  7. Department of Medicine, McGill University, Montréal, Canada

    P N Tonin

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  1. N A L Cody
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Correspondence to P N Tonin.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Cody, N., Ouellet, V., Manderson, E. et al. Transfer of chromosome 3 fragments suppresses tumorigenicity of an ovarian cancer cell line monoallelic for chromosome 3p. Oncogene 26, 618–632 (2007). https://doi.org/10.1038/sj.onc.1209821

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