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Updated: Aug 12, 2026

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

DNA methyltransferase 3b contributes to oncogenic transformation induced by SV40T antigen and activated Ras

Kenzo Soejima1, Weizhao Fang, Barrett J Rollins

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Oncogene
|July 25, 2003
PubMed

Insights

The DNA methyltransferase DNMT3b drives cancer development by silencing tumor suppressor genes. Inhibiting DNMT3b reduces tumor growth and reactivates silenced genes, offering a potential therapeutic target for lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Transcriptional silencing of tumor suppressor genes via DNA methylation is crucial for cancer development.
  • The specific DNA methyltransferases initiating this silencing are not fully understood.

Purpose of the Study:

  • To investigate the role of de novo DNA methyltransferase DNMT3b in malignant transformation and lung cancer.
  • To determine if DNMT3b contributes to the oncogenic phenotype and silences specific tumor suppressor genes.

Main Methods:

  • Utilized normal human bronchial epithelial (NHBE) cells and mouse embryo fibroblasts (MEFs) engineered for transformation.
  • Employed antisense suppression to inhibit DNMT3b expression.
  • Assessed anchorage-independent growth (soft agar assay) and in vivo tumorigenicity.
  • Analyzed the expression and promoter methylation status of tumor suppressor genes (FHIT, TSLC1, RASSF1A).

Main Results:

  • DNMT3b expression was elevated in transformed NHBE cells.
  • Antisense suppression of DNMT3b inhibited soft agar growth in transformed cells.
  • Fibroblasts from Dnmt3b(-/-) mice exhibited significantly reduced tumorigenicity.
  • DNMT3b inhibition led to re-expression of FHIT and TSLC1, with TSLC1 promoter methylation correlating with its silencing.

Conclusions:

  • DNMT3b plays a significant role in malignant transformation and lung cancer development.
  • DNMT3b contributes to the oncogenic phenotype, potentially through direct DNA methylation or chromatin modification.
  • Targeting DNMT3b represents a potential therapeutic strategy for cancers driven by its activity.

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