ERK and AKT signaling drive MED1 overexpression in prostate cancer in association with elevated proliferation and tumorigenicity

Feng Jin, Shazia Irshad, Wei Yu, Madesh Belakavadi, Marina Chekmareva, Michael M. Ittmann, Cory Abate-Shen, Joseph Fondell

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

MED1 is a key coactivator of the androgen receptor (AR) and other signal-activated transcription factors. Whereas MED1 is overexpressed in prostate cancer cell lines and is thought to coactivate distinct target genes involved in cell-cycle progression and castration-resistant growth, the underlying mechanisms by which MED1 becomes overexpressed and its oncogenic role in clinical prostate cancer have remained unclear. Here, we report that MED1 is overexpressed in the epithelium of clinically localized human prostate cancer patients, which correlated with elevated cellular proliferation. In a Nkx3.1:Pten mutant mouse model of prostate cancer that recapitulates the human disease, MED1 protein levels were markedly elevated in the epithelium of both invasive and castration-resistant adenocarcinoma prostate tissues. Mechanistic evidence showed that hyperactivated ERK and/or AKT signaling pathways promoted MED1 overexpression in prostate cancer cells. Notably, ectopic MED1 overexpression in prostate cancer xenografts significantly promoted tumor growth in nude mice. Furthermore, MED1 expression in prostate cancer cells promoted the expression of a number of novel genes involved in inflammation, cell proliferation, and survival. Together, these findings suggest that elevated MED1 is a critical molecular event associated with prostate oncogenesis.

Original languageEnglish (US)
Pages (from-to)736-747
Number of pages12
JournalMolecular Cancer Research
Volume11
Issue number7
DOIs
StatePublished - Jul 1 2013

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Prostatic Neoplasms
Castration
Prostate
Epithelium
Cell Proliferation
Androgen Receptors
Growth
Heterografts
Nude Mice
Genes
Cell Survival
Cell Cycle
Carcinogenesis
Adenocarcinoma
Transcription Factors
Inflammation
Cell Line
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Jin, Feng ; Irshad, Shazia ; Yu, Wei ; Belakavadi, Madesh ; Chekmareva, Marina ; Ittmann, Michael M. ; Abate-Shen, Cory ; Fondell, Joseph. / ERK and AKT signaling drive MED1 overexpression in prostate cancer in association with elevated proliferation and tumorigenicity. In: Molecular Cancer Research. 2013 ; Vol. 11, No. 7. pp. 736-747.
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ERK and AKT signaling drive MED1 overexpression in prostate cancer in association with elevated proliferation and tumorigenicity. / Jin, Feng; Irshad, Shazia; Yu, Wei; Belakavadi, Madesh; Chekmareva, Marina; Ittmann, Michael M.; Abate-Shen, Cory; Fondell, Joseph.

In: Molecular Cancer Research, Vol. 11, No. 7, 01.07.2013, p. 736-747.

Research output: Contribution to journalArticle

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AU - Ittmann, Michael M.

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