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Article Dans Une Revue Scientific Reports Année : 2020

The high protein expression of FOXO3, but not that of FOXO1, is associated with markers of good prognosis

François Lallemand
  • Fonction : Auteur
Sophie Vacher
  • Fonction : Auteur
Leanne De Koning
  • Fonction : Auteur
Ambre Petitalot
  • Fonction : Auteur
Adrien Briaux
  • Fonction : Auteur
Keltouma Driouch
  • Fonction : Auteur
Céline Callens
  • Fonction : Auteur
Anne Schnitzler
  • Fonction : Auteur
Caroline Lecerf
  • Fonction : Auteur
Floriane Oulie-Bard
  • Fonction : Auteur
Aurélie Barbet
  • Fonction : Auteur
Anne Vincent
Bernard S. Lopez
Rosette Lidereau
  • Fonction : Auteur
Ivan Bieche
  • Fonction : Auteur
Sandrine M. Caputo
  • Fonction : Auteur

Résumé

To better define the role of FOXO1 and FOXO3 transcriptional factors in breast carcinogenesis, we performed a comparative study of their expression at both the RNA and protein levels in a series of human breast tumors. We used qRT-PCR assay to quantify mRNA expression and Reverse Phase Protein Arrays (RPPA) to quantify protein expression in 218 breast tumors from patients with known clinical/pathological status and outcome. Weak correlations were observed between mRNA and protein expressions for both FOXO1 and FOXO3 genes. High expression of FOXO3 protein, but not FOXO1 protein, was a good prognostic marker, negatively correlated with KI67 and markers of activity of the PI3K/AKT/mTOR oncogenic pathway, and positively correlated with p53, a marker of apoptosis. Moreover, FOXO3 protein expression, but not FOXO1 protein expression, was also negatively correlated with various proteins involved in different DNA repair mechanisms. FOXO3 protein, but not FOXO1 protein, appears to be a tumor suppressor that inhibits breast cancer by altering DNA damage response (DDR), thereby inducing p53-dependent apoptosis. This antitumor effect appears to be suppressed by excessive activity of the PI3K/AKT/mTOR pathway. High FOXO3 protein expression could be a biomarker of deficient DDR in breast tumors.

Dates et versions

hal-02571409 , version 1 (12-05-2020)

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Citer

François Lallemand, Sophie Vacher, Leanne De Koning, Ambre Petitalot, Adrien Briaux, et al.. The high protein expression of FOXO3, but not that of FOXO1, is associated with markers of good prognosis. Scientific Reports, 2020, 10 (1), pp.6920. ⟨10.1038/s41598-020-63895-8⟩. ⟨hal-02571409⟩
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