Related Experiment Video

Updated: Jun 27, 2026

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
06:24

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line

Published on: April 11, 2025

Epigenetic regulation and molecular characterization of C/EBPalpha in pancreatic cancer cells

Takashi Kumagai1, Tadayuki Akagi, Julian C Desmond

  • 1Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA. kumamed1_2001@yahoo.co.jp

International Journal of Cancer
|November 28, 2008
PubMed

Insights

Epigenetic silencing of the C/EBPalpha gene contributes to pancreatic cancer progression. Restoring C/EBPalpha expression suppressed tumor cell proliferation, identifying it as a potential therapeutic target for pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Pancreatic cancer is a challenging disease with limited therapeutic options.
  • Epigenetic modifications, including DNA methylation and histone deacetylation, are key mechanisms for tumor suppressor gene silencing in cancer.
  • Identifying epigenetically silenced genes is crucial for developing novel molecular-targeted therapies for pancreatic cancer.

Purpose of the Study:

  • To identify epigenetically silenced genes in pancreatic cancer cells.
  • To investigate the role of C/EBPalpha as a potential tumor suppressor gene in pancreatic cancer.
  • To explore the therapeutic potential of targeting epigenetic silencing in pancreatic cancer.

Main Methods:

  • Pancreatic cancer cells (PANC-1) were treated with DNA methyltransferase inhibitor (5Aza-dC) and histone deacetylase inhibitor (SAHA).
  • Oligonucleotide microarray and real-time PCR were used to identify and validate gene expression changes.
  • Chromatin immunoprecipitation, bisulfate sequencing, co-immunoprecipitation, and immunohistochemistry were employed to study C/EBPalpha regulation and function.

Main Results:

  • Treatment with 5Aza-dC and SAHA upregulated several genes, including C/EBPalpha, in pancreatic cancer cells.
  • C/EBPalpha expression was restored in multiple pancreatic cancer cell lines, with evidence of promoter hypomethylation and histone acetylation.
  • Forced expression of C/EBPalpha suppressed pancreatic cancer cell proliferation and inhibited E2F1 transcriptional activity.
  • C/EBPalpha exhibited aberrant cytoplasmic localization in pancreatic cancer cells compared to nuclear localization in normal cells.

Conclusions:

  • Aberrant epigenetic silencing and inappropriate cytoplasmic localization of C/EBPalpha contribute to its functional dysregulation in pancreatic cancer.
  • C/EBPalpha acts as a novel candidate tumor suppressor gene in pancreatic cancer.
  • Targeting epigenetic modifications to restore C/EBPalpha function presents a promising therapeutic strategy for pancreatic cancer.

More Related Videos

Generating the Transcriptional Regulation View of Transcriptomic Features for Prediction Task and Dark Biomarker Detection on Small Datasets03:37

Generating the Transcriptional Regulation View of Transcriptomic Features for Prediction Task and Dark Biomarker Detection on Small Datasets

Published on: March 1, 2024

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker07:47

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker

Published on: September 15, 2023

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...