SRC increases MYC mRNA expression in estrogen receptor-positive breast cancer via mRNA stabilization and inhibition of p53 function

Christopher Abdullah, Hasan Korkaya, Shinji Iizuka, Sara A. Courtneidge

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The transcription factor gene MYC is important in breast cancer, and its mRNA is maintained at a high level even in the absence of gene amplification. The mechanism(s) underlying increased MYC mRNA expression is unknown. Here, we demonstrate that MYC mRNA was stabilized upon estrogen stimulation of estrogen receptor-positive breast cancer cells via SRC-dependent effects on a recently described RNA-binding protein, IMP1 with an N-terminal deletion (ΔN-IMP1). We also show that loss of the tumor suppressor p53 increased MYC mRNA levels even in the absence of estrogen stimulation. However, in cells with wild-type p53, SRC acted to overcome p53-mediated inhibition of estrogen-stimulated cell cycle entry and progression. SRC thus promotes cell proliferation in two ways: by stabilizing MYC mRNA and by inhibiting p53 function. Since estrogen receptor-positive breast cancers typically express wild-type p53, these studies establish a rationale for p53 status to be predictive for effective SRC inhibitor treatment in this subtype of breast cancer.

Original languageEnglish (US)
Article numbere00463-17
JournalMolecular and Cellular Biology
Volume38
Issue number6
DOIs
StatePublished - Mar 1 2018

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Estrogen Receptors
Breast Neoplasms
Messenger RNA
Estrogens
RNA-Binding Proteins
Gene Amplification
Cell Cycle
Transcription Factors
Cell Proliferation
Genes
Neoplasms

Keywords

  • Breast cancer
  • C-myc
  • Estrogen
  • P53
  • SRC

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

SRC increases MYC mRNA expression in estrogen receptor-positive breast cancer via mRNA stabilization and inhibition of p53 function. / Abdullah, Christopher; Korkaya, Hasan; Iizuka, Shinji; Courtneidge, Sara A.

In: Molecular and Cellular Biology, Vol. 38, No. 6, e00463-17, 01.03.2018.

Research output: Contribution to journalArticle

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