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Updated: Aug 20, 2026

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model
Published on: June 11, 2014
FRA-1 expression level regulates proliferation and invasiveness of breast cancer cells
Karine Belguise1, Nathalie Kersual, Florence Galtier
1Inserm U540, Endocrinologie Moléculaire et Cellulaire des Cancers, 60 Rue de Navacelles, 34090 Montpellier, France.
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 beta1-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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