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FRA-1 expression level regulates proliferation and invasiveness of breast cancer cells

Oncogene volume 24, pages 1434–1444 (2005)Cite this article

Abstract

Breast cancer progression is likely a multistep process involving the activation and inactivation of a number of genes. Previously, we showed that the mRNA coding for Fra-1, a FOS family member and an AP-1 transcription factor component, was highly expressed in the more invasive estrogen receptor negative (ER−) breast cancer cell lines. We used a tet-off system to stably overexpress Fra-1 in MCF7 ER+ cells and evaluate the impact of Fra-1 on this aggressive phenotype. Conversely, Fra-1 was silenced in highly invasive ER−MDA-MB231 cells using RNA interference. We report that in both systems the Fra-1 expression level was positively associated with cell proliferation, cell motility and invasiveness assessed in vitro. In addition, Fra-1 inhibition in fibroblastoid ER− cells, which formed colonies with large stellate projections in Matrigel, resulted in morphological changes. Cells acquired an epithelioid shape and had a spherical appearance in Matrigel. Fra-1 regulated several genes, implicated in invasion, angiogenesis and cell proliferation independently of β1-integrin activation, and directly induced MMP-1 and MMP-9 promoter activity. These overall results show that high Fra-1 expression is associated with a more malignant cell phenotype and suggest that Fra-1 could have a pivotal role in breast cancer progression.

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Article Open access 16 December 2023

Gian Luca Rampioni Vinciguerra, Marina Capece, … Carlo M. Croce

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Acknowledgements

We thank N Lautredou from the Imaging Service of the IGH (Montpellier) and C Duperray from the Flow Cytometry Service of Inserm (Montpellier) for their support, J-Y Cance for photographs and G Freiss and F Vignon for critical reading of the manuscript. We are grateful to CE Brinckerhoff and DD Boyd for providing plasmids. This work was supported by the ‘Institut National de la Santé et de la Recherche Médicale’, the ‘Association pour la Recherche sur le Cancer’ (Grant no. 5825), the French ‘Ministère de la Recherche et de l’Enseignement Supérieur’ (fellowship to NK), la Fondation pour la Recherche Médicale et la Ligue Nationale Contre le Cancer (fellowships to KB).

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  1. Inserm U540, Endocrinologie Moléculaire et Cellulaire des Cancers, 60 Rue de Navacelles, 34090, Montpellier, France

    Karine Belguise, Nathalie Kersual, Florence Galtier & Dany Chalbos

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  1. Karine Belguise
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  2. Nathalie Kersual
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Correspondence to Dany Chalbos.

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Belguise, K., Kersual, N., Galtier, F. et al. FRA-1 expression level regulates proliferation and invasiveness of breast cancer cells. Oncogene 24, 1434–1444 (2005). https://doi.org/10.1038/sj.onc.1208312

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