Argonaute 2 expression correlates with a Luminal B breast cancer subtype and induces estrogen receptor alpha isoform variation

Adrienne K. Conger, Elizabeth C. Martin, Thomas J. Yan, Lyndsay V. Rhodes, Van T. Hoang, Jacqueline La, Muralidharan Anbalagan, Hope E. Burks, Brian G. Rowan, Kenneth Nephew, Bridgette M. Collins-Burow, Matthew E. Burow

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Estrogen receptor alpha (ERα) signaling pathways are frequently disrupted in breast cancer and contribute to disease progression. ERα signaling is multifaceted and many ERα regulators have been identified including transcription factors and growth factor pathways. More recently, microRNAs (miRNAs) are shown to deregulate ERα activity in breast carcinomas, with alterations in both ERα and miRNA expression correlating to cancer progression. In this study, we show that a high expression of Argonaute 2 (AGO2), a translation regulatory protein and mediator of miRNA function, correlates with the luminal B breast cancer subtype. We further demonstrate that a high expression of AGO2 in ERα+ tumors correlates with a poor clinical outcome. MCF-7 breast cancer cells overexpressing AGO2 (MCF7-AGO2) altered ERα downstream signaling and selective ERα variant expression. Enhanced ERα-36, a 36 kDa ERα isoform, protein and gene expression was observed in vitro. Through quantitative polymerase chain reaction (qPCR), we demonstrate decreased basal expression of the full-length ERα and progesterone receptor genes, in addition to loss of estrogen stimulated gene expression in vitro. Despite the loss, MCF-7-AGO2 cells demonstrated increased estrogen stimulated tumorigenesis in vivo. Together with our clinical findings on AGO2 expression and the luminal B subtype, we suggest that AGO2 is a regulator of altered ERα signaling in breast tumors.

Original languageEnglish (US)
Article number8
JournalNon-coding RNA
Volume2
Issue number3
DOIs
StatePublished - Sep 21 2016

Fingerprint

Estrogen Receptor alpha
Protein Isoforms
Breast Neoplasms
MicroRNAs
Gene expression
Tumors
Estrogens
Gene Expression
Polymerase chain reaction
Protein Biosynthesis
Progesterone Receptors
Disease Progression
Neoplasms
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Transcription Factors
Genes
Cells

Keywords

  • AGO2
  • Estrogen receptor
  • Isoform
  • Luminal B
  • MiRNA

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Molecular Biology

Cite this

Conger, A. K., Martin, E. C., Yan, T. J., Rhodes, L. V., Hoang, V. T., La, J., ... Burow, M. E. (2016). Argonaute 2 expression correlates with a Luminal B breast cancer subtype and induces estrogen receptor alpha isoform variation. Non-coding RNA, 2(3), [8]. https://doi.org/10.3390/ncrna2030008

Argonaute 2 expression correlates with a Luminal B breast cancer subtype and induces estrogen receptor alpha isoform variation. / Conger, Adrienne K.; Martin, Elizabeth C.; Yan, Thomas J.; Rhodes, Lyndsay V.; Hoang, Van T.; La, Jacqueline; Anbalagan, Muralidharan; Burks, Hope E.; Rowan, Brian G.; Nephew, Kenneth; Collins-Burow, Bridgette M.; Burow, Matthew E.

In: Non-coding RNA, Vol. 2, No. 3, 8, 21.09.2016.

Research output: Contribution to journalArticle

Conger, AK, Martin, EC, Yan, TJ, Rhodes, LV, Hoang, VT, La, J, Anbalagan, M, Burks, HE, Rowan, BG, Nephew, K, Collins-Burow, BM & Burow, ME 2016, 'Argonaute 2 expression correlates with a Luminal B breast cancer subtype and induces estrogen receptor alpha isoform variation', Non-coding RNA, vol. 2, no. 3, 8. https://doi.org/10.3390/ncrna2030008
Conger, Adrienne K. ; Martin, Elizabeth C. ; Yan, Thomas J. ; Rhodes, Lyndsay V. ; Hoang, Van T. ; La, Jacqueline ; Anbalagan, Muralidharan ; Burks, Hope E. ; Rowan, Brian G. ; Nephew, Kenneth ; Collins-Burow, Bridgette M. ; Burow, Matthew E. / Argonaute 2 expression correlates with a Luminal B breast cancer subtype and induces estrogen receptor alpha isoform variation. In: Non-coding RNA. 2016 ; Vol. 2, No. 3.
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