Related Experiment Video

Updated: Aug 25, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Epigenetic inactivation of TMS1/ASC in ovarian cancer

Katsuhiko Terasawa1, Satoru Sagae, Minoru Toyota

  • 1Departments of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan. kterasaw@sapmed.ac.jp

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 26, 2004
PubMed
Abstract

Insights

Epigenetic silencing of the TMS1/ASC gene through DNA methylation and histone deacetylation promotes ovarian cancer cell survival. Aberrant methylation of TMS1/ASC is common in ovarian tumors, especially clear cell types.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Ovarian cancer progression involves complex genetic and epigenetic alterations.
  • Apoptotic pathways are frequently dysregulated in cancer, contributing to tumor cell survival.
  • Epigenetic silencing of tumor suppressor genes is a key mechanism in tumorigenesis.

Purpose of the Study:

  • To investigate the epigenetic inactivation of apoptotic pathways in ovarian cancer.
  • To examine DNA methylation and gene expression of proapoptotic genes in ovarian cancers.
  • To correlate epigenetic alterations with clinicopathological features of ovarian cancer patients.

Main Methods:

  • DNA methylation analysis using combined bisulfite restriction analysis.
  • Gene expression profiling via reverse transcription-polymerase chain reaction (RT-PCR).
  • Histone acetylation assessment using chromatin immunoprecipitation.

Main Results:

  • TMS1/ASC gene expression was absent in 6/15 ovarian cancer cell lines.
  • Dense DNA methylation and histone deacetylation were associated with TMS1/ASC silencing.
  • Aberrant TMS1/ASC methylation occurred in 19% of primary ovarian cancers, significantly higher in clear cell types.

Conclusions:

  • Methylation-mediated silencing of TMS1/ASC enables ovarian cancer cells to evade apoptosis, conferring a survival advantage.
  • Aberrant methylation of TMS1/ASC plays a significant role in ovarian tumorigenesis, particularly in clear cell ovarian cancers.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Related Concept Videos

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...
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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...