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Suppression of non-small cell lung cancer proliferation and tumorigenicity by DENND2D

Bing Ling1, Hongwei Zheng, Guobin Fu

  • 1State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, PR China.

Lung Cancer (Amsterdam, Netherlands)
|November 28, 2012
PubMed

Insights

DENND2D down-regulation is an early event in lung cancer development. Restoring DENND2D expression suppresses non-small cell lung cancer cell proliferation by inducing apoptosis, suggesting its tumor suppressor role.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • DENND2D (DENN domain containing 2D) was identified as downregulated in lung cancer via suppression subtractive hybridization (SSH).
  • DENND2D downregulation is observed in non-small cell lung cancer (NSCLC) cell lines, lung squamous cell carcinoma (SCC) tissues, and precancerous lesions.

Purpose of the Study:

  • To investigate the role of DENND2D in lung cancer development and progression.
  • To elucidate the regulatory network of DENND2D at genomic, transcriptional, and translational levels.
  • To assess the therapeutic potential of DENND2D in NSCLC.

Main Methods:

  • Suppression subtractive hybridization (SSH) library construction.
  • In vitro analysis of DNA copy number, mRNA, and protein expression levels.
  • In vitro and in vivo proliferation assays of NSCLC cells with DENND2D overexpression.
  • Apoptosis induction assays.

Main Results:

  • DENND2D downregulation occurs early in lung cancer, even in precancerous lesions.
  • A complex regulatory network governs DENND2D expression.
  • Overexpression of DENND2D significantly inhibited NSCLC cell proliferation both in vitro and in vivo.
  • DENND2D overexpression induced apoptosis in NSCLC cells.

Conclusions:

  • DENND2D acts as a tumor suppressor-like gene, preventing the survival and expansion of genetically damaged cells via apoptosis.
  • Absence of DENND2D may facilitate early tumorigenesis in the lung.
  • DENND2D warrants further investigation as a potential therapeutic target for lung cancer.

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