Open Access

A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays

  • Authors:
    • Sanjib Chaudhary
    • B. Madhu Krishna
    • Sandip K. Mishra
  • View Affiliations

  • Published online on: June 7, 2017     https://doi.org/10.3892/ol.2017.6329
  • Pages: 1247-1264
  • Copyright: © Chaudhary et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Forkhead box protein A1 (FOXA1) is essential for the growth and differentiation of breast epithelium, and has a favorable outcome in breast cancer (BC). Elevated FOXA1 expression in BC also facilitates hormone responsiveness in estrogen receptor (ESR)‑positive BC. However, the interaction between these two pathways is not fully understood. FOXA1 and GATA binding protein 3 (GATA3) along with ESR1 expression are responsible for maintaining a luminal phenotype, thus suggesting the existence of a strong association between them. The present study utilized the Oncomine™ microarray database to identify FOXA1:ESR1 and FOXA1:ESR1:GATA3 co‑expression co‑regulated genes. Oncomine™ analysis revealed 115 and 79 overlapping genes clusters in FOXA1:ESR1 and FOXA1:ESR1:GATA3 microarrays, respectively. Five ESR1 direct target genes [trefoil factor 1 (TFF1/PS2), B-cell lymphoma 2 (BCL2), seven in absentia homolog 2 (SIAH2), cellular myeloblastosis viral oncogene homolog (CMYB) and progesterone receptor (PGR)] were detected in the co‑expression clusters. To further investigate the role of FOXA1 in ESR1‑positive cells, MCF7 cells were transfected with a FOXA1 expression plasmid, and it was observed that the direct target genes of ESR1 (PS2, BCL2, SIAH2 and PGR) were significantly regulated upon transfection. Analysis of one of these target genes, PS2, revealed the presence of two FOXA1 binding sites in the vicinity of the estrogen response element (ERE), which was confirmed by binding assays. Under estrogen stimulation, FOXA1 protein was recruited to the FOXA1 site and could also bind to the ERE site (although in minimal amounts) in the PS2 promoter. Co‑transfection of FOXA1/ESR1 expression plasmids demonstrated a significantly regulation of the target genes identified in the FOXA1/ESR1 multi‑arrays compared with only FOXA1 transfection, which was suggestive of a synergistic effect of ESR1 and FOXA1 on the target genes. In summary, the present study identified novel FOXA1, ESR1 and GATA3 co‑expressed genes that may be involved in breast tumorigenesis.
View Figures
View References

Related Articles

Journal Cover

August-2017
Volume 14 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chaudhary S, Krishna BM and Mishra SK: A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays. Oncol Lett 14: 1247-1264, 2017
APA
Chaudhary, S., Krishna, B.M., & Mishra, S.K. (2017). A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays. Oncology Letters, 14, 1247-1264. https://doi.org/10.3892/ol.2017.6329
MLA
Chaudhary, S., Krishna, B. M., Mishra, S. K."A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays". Oncology Letters 14.2 (2017): 1247-1264.
Chicago
Chaudhary, S., Krishna, B. M., Mishra, S. K."A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays". Oncology Letters 14, no. 2 (2017): 1247-1264. https://doi.org/10.3892/ol.2017.6329