Eph receptor B4 is a regulator of estrogen receptor alpha in breast cancer cells.

Abstract

BACKGROUND:

Estrogen receptor alpha (ER-α) plays an important role in breast cancer initiation and progression and represents a major target in cancer therapy. The expression and activity of ER-α is regulated by multiple mechanisms at the transcriptional and post-translational level. Interaction of tyrosine kinase receptor-activated signaling pathways with ER-α function has been reported. We previously performed a kinome-wide small interfering RNA high-throughput screen to identify novel protein kinases involved in the regulation of ER-α transcriptional activity in human breast cancer cells. Our screening analysis identified the Eph receptor tyrosine kinases (Eph) as potential positive regulators of ER-α.

RESULTS:

In this study, we demonstrate Eph receptor B4 (EphB4), a member of Eph kinase family, a positive regulator of ER-α in human breast cancer cell lines (MCF-7, T-47D and BT-474). Down-regulation of EphB4 by RNA interference technology impairs estrogen-dependent ER-α transcriptional activity in breast cancer cells. Decreased activity of ER-α after EphB4 knockdown is the consequence of diminished ER-α messenger RNA and protein expression. Furthermore, phosphorylation of Akt, a downstream mediator of EphB4, is reduced following EphB4 silencing.

CONCLUSIONS:

Our data suggests EphB4 as an upstream regulator of ER-α in human breast cancer cells by modulating ER-α transcription. The results also suggest Akt as a relevant downstream signaling molecule in this novel EphB4-ER-α pathway.

• Authors: Fee Schmitt, Phuong-Hien Nguyen, Nibedita Gupta, Doris Mayer
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 33 Issue 4 Pg. 244-8 (Aug 2013) ISSN: 1532-4281 [Electronic] England
• PMID: 23725356 (Publication Type: Journal Article)

Chemical References

• Estrogen Receptor alpha
• RNA, Small Interfering
• Receptors, Eph Family
• Proto-Oncogene Proteins c-akt

Topics

• Breast Neoplasms (genetics, pathology)
• Estrogen Receptor alpha (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MCF-7 Cells
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Small Interfering (genetics)
• Receptors, Eph Family (genetics, metabolism)
• Signal Transduction