Amplitude modulation of androgen signaling by c-MYC

Min Ni, Yiwen Chen, Teng Fei, Dan Li, Elgene Lim, X. Shirley Liu, Myles Brown

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Androgen-stimulated growth of the molecular apocrine breast cancer subtype is mediated by an androgen receptor (AR)-regulated transcriptional program. However, the molecular details of this AR-centered regulatory network and the roles of other transcription factors that cooperate with AR in the network remain elusive. Here we report a positive feed-forward loop that enhances breast cancer growth involving AR, AR coregulators, and downstream target genes. In the absence of an androgen signal, TCF7L2 interacts with FOXA1 at AR-binding sites and represses the basal expression of AR target genes, including MYC. Direct AR regulation of MYC cooperates with AR-mediated activation of HER2/HER3 signaling. HER2/HER3 signaling increases the transcriptional activity of MYC through phosphorylation of MAD1, leading to increased levels of MYC/MAX heterodimers. MYC in turn reinforces the transcriptional activation of androgen-responsive genes. These results reveal a novel regulatory network in molecular apocrine breast cancers regulated by androgen and AR in which MYC plays a central role as both a key target and a cooperating transcription factor to drive oncogenic growth.

Original languageEnglish (US)
Pages (from-to)734-748
Number of pages15
JournalGenes and Development
Volume27
Issue number7
DOIs
StatePublished - Apr 1 2013

Fingerprint

Androgen Receptors
Androgens
Breast Neoplasms
Transcription Factors
Growth
Genes
Transcriptional Activation
Binding Sites
Phosphorylation

Keywords

  • AR
  • Breast cancer
  • Cistrome
  • FOXA1
  • MYC
  • TCF7L2

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Ni, M., Chen, Y., Fei, T., Li, D., Lim, E., Liu, X. S., & Brown, M. (2013). Amplitude modulation of androgen signaling by c-MYC. Genes and Development, 27(7), 734-748. https://doi.org/10.1101/gad.209569.112

Amplitude modulation of androgen signaling by c-MYC. / Ni, Min; Chen, Yiwen; Fei, Teng; Li, Dan; Lim, Elgene; Liu, X. Shirley; Brown, Myles.

In: Genes and Development, Vol. 27, No. 7, 01.04.2013, p. 734-748.

Research output: Contribution to journalArticle

Ni, M, Chen, Y, Fei, T, Li, D, Lim, E, Liu, XS & Brown, M 2013, 'Amplitude modulation of androgen signaling by c-MYC', Genes and Development, vol. 27, no. 7, pp. 734-748. https://doi.org/10.1101/gad.209569.112
Ni, Min ; Chen, Yiwen ; Fei, Teng ; Li, Dan ; Lim, Elgene ; Liu, X. Shirley ; Brown, Myles. / Amplitude modulation of androgen signaling by c-MYC. In: Genes and Development. 2013 ; Vol. 27, No. 7. pp. 734-748.
@article{353bf42eef3742cfb2c9c2b6ffe8561c,
title = "Amplitude modulation of androgen signaling by c-MYC",
abstract = "Androgen-stimulated growth of the molecular apocrine breast cancer subtype is mediated by an androgen receptor (AR)-regulated transcriptional program. However, the molecular details of this AR-centered regulatory network and the roles of other transcription factors that cooperate with AR in the network remain elusive. Here we report a positive feed-forward loop that enhances breast cancer growth involving AR, AR coregulators, and downstream target genes. In the absence of an androgen signal, TCF7L2 interacts with FOXA1 at AR-binding sites and represses the basal expression of AR target genes, including MYC. Direct AR regulation of MYC cooperates with AR-mediated activation of HER2/HER3 signaling. HER2/HER3 signaling increases the transcriptional activity of MYC through phosphorylation of MAD1, leading to increased levels of MYC/MAX heterodimers. MYC in turn reinforces the transcriptional activation of androgen-responsive genes. These results reveal a novel regulatory network in molecular apocrine breast cancers regulated by androgen and AR in which MYC plays a central role as both a key target and a cooperating transcription factor to drive oncogenic growth.",
keywords = "AR, Breast cancer, Cistrome, FOXA1, MYC, TCF7L2",
author = "Min Ni and Yiwen Chen and Teng Fei and Dan Li and Elgene Lim and Liu, {X. Shirley} and Myles Brown",
year = "2013",
month = "4",
day = "1",
doi = "10.1101/gad.209569.112",
language = "English (US)",
volume = "27",
pages = "734--748",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "7",

}

TY - JOUR

T1 - Amplitude modulation of androgen signaling by c-MYC

AU - Ni, Min

AU - Chen, Yiwen

AU - Fei, Teng

AU - Li, Dan

AU - Lim, Elgene

AU - Liu, X. Shirley

AU - Brown, Myles

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Androgen-stimulated growth of the molecular apocrine breast cancer subtype is mediated by an androgen receptor (AR)-regulated transcriptional program. However, the molecular details of this AR-centered regulatory network and the roles of other transcription factors that cooperate with AR in the network remain elusive. Here we report a positive feed-forward loop that enhances breast cancer growth involving AR, AR coregulators, and downstream target genes. In the absence of an androgen signal, TCF7L2 interacts with FOXA1 at AR-binding sites and represses the basal expression of AR target genes, including MYC. Direct AR regulation of MYC cooperates with AR-mediated activation of HER2/HER3 signaling. HER2/HER3 signaling increases the transcriptional activity of MYC through phosphorylation of MAD1, leading to increased levels of MYC/MAX heterodimers. MYC in turn reinforces the transcriptional activation of androgen-responsive genes. These results reveal a novel regulatory network in molecular apocrine breast cancers regulated by androgen and AR in which MYC plays a central role as both a key target and a cooperating transcription factor to drive oncogenic growth.

AB - Androgen-stimulated growth of the molecular apocrine breast cancer subtype is mediated by an androgen receptor (AR)-regulated transcriptional program. However, the molecular details of this AR-centered regulatory network and the roles of other transcription factors that cooperate with AR in the network remain elusive. Here we report a positive feed-forward loop that enhances breast cancer growth involving AR, AR coregulators, and downstream target genes. In the absence of an androgen signal, TCF7L2 interacts with FOXA1 at AR-binding sites and represses the basal expression of AR target genes, including MYC. Direct AR regulation of MYC cooperates with AR-mediated activation of HER2/HER3 signaling. HER2/HER3 signaling increases the transcriptional activity of MYC through phosphorylation of MAD1, leading to increased levels of MYC/MAX heterodimers. MYC in turn reinforces the transcriptional activation of androgen-responsive genes. These results reveal a novel regulatory network in molecular apocrine breast cancers regulated by androgen and AR in which MYC plays a central role as both a key target and a cooperating transcription factor to drive oncogenic growth.

KW - AR

KW - Breast cancer

KW - Cistrome

KW - FOXA1

KW - MYC

KW - TCF7L2

UR - http://www.scopus.com/inward/record.url?scp=84876217788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876217788&partnerID=8YFLogxK

U2 - 10.1101/gad.209569.112

DO - 10.1101/gad.209569.112

M3 - Article

C2 - 23530127

AN - SCOPUS:84876217788

VL - 27

SP - 734

EP - 748

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 7

ER -