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

Abstract

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.

• Authors: François Lallemand, Sophie Vacher, Leanne de Koning, Ambre Petitalot, Adrien Briaux, Keltouma Driouch, Céline Callens, Anne Schnitzler, Caroline Lecerf, Floriane Oulie-Bard, Aurélie Barbet, Anne Vincent, Sophie Zinn-Justin, Bernard S Lopez, Rosette Lidereau, Ivan Bieche, Sandrine M Caputo
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 6920 (04 24 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32332845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• FOXO1 protein, human
• FOXO3 protein, human
• Forkhead Box Protein O1
• Forkhead Box Protein O3
• RNA, Messenger
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Adult
• Aged
• Aged, 80 and over
• Apoptosis (genetics)
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (diagnosis, genetics, pathology)
• Cell Cycle (genetics)
• Cell Proliferation (genetics)
• DNA Damage (genetics)
• DNA Repair (genetics)
• Female
• Forkhead Box Protein O1 (genetics, metabolism)
• Forkhead Box Protein O3 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Phosphatidylinositol 3-Kinases (metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (genetics, metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)