Related Experiment Video

Updated: Sep 27, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

Decrease of DNA methyltransferase 1 expression relative to cell proliferation in transitional cell carcinoma

Fumihiro Kimura1, Hans-Helge Seifert, Andrea R Florl

  • 1Urologische Klinik, Heinrich-Heine-Universität Düsseldorf, Germany.

International Journal of Cancer
|February 21, 2003
PubMed

Insights

In bladder cancer, DNA methyltransferase I (DNMT1) expression is reduced relative to cell proliferation, contributing to DNA hypomethylation. However, this downregulation doesn't solely determine the extent of hypomethylation in transitional cell carcinoma (TCC).

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Common cancers like transitional cell carcinoma (TCC) exhibit both gene hypermethylation and global DNA hypomethylation.
  • Genome-wide hypomethylation primarily impacts repetitive sequences, such as LINE-1 retrotransposons, crucial for genomic stability.
  • Proper methylation of repetitive sequences relies on adequate DNA methyltransferase I (DNMT1) expression during DNA replication.

Purpose of the Study:

  • To investigate the expression of DNMT1 relative to cell proliferation in TCC and renal cell carcinoma (RCC) cell lines and tissues.
  • To understand the role of DNMT1 downregulation in DNA hypomethylation observed in these cancers.
  • To explore the expression patterns of de novo methyltransferases DNMT3A and DNMT3B in TCC and RCC.

Main Methods:

  • Analysis of DNMT1 mRNA and protein levels in cancer cell lines and tissues relative to the proliferation marker PCNA.
  • Assessment of DNA hypomethylation using LINE-1 methylation levels.
  • Reporter gene assays to evaluate DNMT1 promoter regulation.
  • Quantitative analysis of DNMT3A and DNMT3B mRNA expression.

Main Results:

  • All tested tumor cell lines showed decreased DNMT1 expression relative to PCNA, alongside DNA hypomethylation.
  • The extent of DNMT1 downregulation did not correlate with the degree of DNA hypomethylation.
  • DNMT1:PCNA mRNA ratios were diminished in a significant portion of TCC tissues, but this also lacked correlation with hypomethylation.
  • DNMT3B was overexpressed in about half of high-stage TCC, and DNMT3A/DNMT3B were generally higher in RCC than TCC lines.

Conclusions:

  • DNMT1 expression does not adequately increase with cell proliferation in bladder cancer, likely contributing to repetitive DNA hypomethylation.
  • The relative DNMT1 downregulation is a factor in hypomethylation but does not solely dictate its extent.
  • DNMT3B overexpression may play a role in advanced TCC, suggesting complex epigenetic dysregulation in these cancers.

More Related Videos

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images09:42

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Published on: September 7, 2017

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...