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Expression of Transgenes in Native Bladder Urothelium Using Adenovirus-Mediated Transduction
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The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor

Chien-Feng Li1,2,3, Wen-Jeng Wu4,5,6,7, Wen-Ren Wu8

  • 1Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.

Oncotarget
|May 6, 2015
PubMed

Insights

The EMP2 gene acts as a tumor suppressor in urothelial carcinoma by halting cell cycle progression. Genistein treatment activates CREB1, which then boosts EMP2 expression, inhibiting tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Urinary bladder urothelial carcinoma (UBUC) is a significant health concern.
  • The role of EMP2 in UBUC progression requires further elucidation.
  • Understanding molecular pathways is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the tumor suppressor role of EMP2 in UBUC.
  • To explore the regulatory mechanism of EMP2 expression by CREB1 and genistein.
  • To assess the prognostic significance of EMP2 in UBUC patients.

Main Methods:

  • Cell culture of UBUC-derived cell lines.
  • Gene expression analysis (transcription and translation).
  • Reporter assays, mutagenesis, and Western blotting.
  • Immunohistochemistry and survival analysis.
  • In vivo xenograft models in mice.

Main Results:

  • EMP2 induces G2/M cell cycle arrest and suppresses UBUC cell viability, proliferation, and anchorage-independent growth.
  • Genistein and CREB1 expression upregulate EMP2 transcription and translation.
  • EMP2 immunointensity correlates with favorable clinicopathological features and survival.
  • Low EMP2 expression is an independent predictor of poor disease-specific survival.
  • Genistein treatment inhibits tumor growth in vivo by upregulating CREB1 and EMP2.

Conclusions:

  • EMP2 functions as a tumor suppressor in UBUC by regulating cell cycle checkpoints.
  • CREB1 acts as a transcriptional activator of EMP2, and genistein enhances this pathway.
  • EMP2 is a novel prognostic biomarker and potential therapeutic target for UBUC.
Keywords:
CREB1EMP2tumor suppressorurinary bladder urothelial carcinoma

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