Sam-pointed domain containing Ets transcription factor in luminal breast cancer pathogenesis

Ashwani K. Sood, Jianmin Wang, Paulette Mhawech-Fauceglia, Bagirathan Jana, Ping Liang, Joseph Geradts

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

We previously described frequent overexpression of Sam-pointed domain containing Ets transcription factor (SPDEF), also known as PDEF, in human breast cancer, and suggested a role for this transcription factor in breast tumor progression. To seek evidence in support of this hypothesis, the MCF-12A breast epithelial cell line was transfected with an SPDEF expression plasmid or with control vector plasmid and the transfected cells tested for their tumorigenic growth in vivo. The data showed that SPDEF expression in MCF-12A cells induced accelerated tumor growth in severe combined immune deficient mice compared with vector-transfected MCF-12A cells. Furthermore, Gene Expression Omnibus and Oncomine databases were mined to determine any correlation between SPDEF expression levels and clinical outcome. High SPDEF expression correlated with poor overall survival of patients with estrogen receptor+ breast cancer, in three independent data sets. In contrast, little correlation was observed between SPDEF expression and cancer relapse or remote metastases. SPDEF expression was further found to be restricted to tumors arising in the luminal epithelial lineage including estrogen receptor+ luminal subtype breast tumors, Her2/neupositive tumors, and apocrine carcinomas. In contrast, little SPDEF expression was found in the basal subtype of breast tumors. Based on these results, we hypothesize that SPDEF has a function in the specification of the progenitor cells of the luminal epithelial lineage that become targets of oncogenesis in luminal breast cancer.

Original languageEnglish (US)
Pages (from-to)1899-1903
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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