Related Experiment Video

Updated: Aug 10, 2025

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes
10:26

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes

Published on: January 16, 2015

8.5K

The epigenetic EZH2/H3K27me3 axis modulates lactotroph tumor cell proliferation

N Zlocowski1, L D V Sosa1, B De la Cruz-Thea2

  • 1Centro de Microscopía Electrónica, Facultad de Ciencias Médicas (CME-FCM) - Instituto de Investigaciones en Ciencias de la Salud, Consejo Nacional de Investigaciones Científicas Técnicas (INICSA-CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaFacultad de Ciencias Médicas (CME-FCM) - Instituto de Investigaciones en Ciencias de la Salud, Consejo Nacional de Investigaciones Científicas Técnicas (INICSA-CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina.

The Journal of Endocrinology
|February 14, 2023
PubMed

Insights

Epigenetic modifications, specifically the EZH2/H3K27me3 axis, drive prolactin (PRL) pituitary neuroendocrine tumor (PitNET) cell proliferation. Inhibiting this axis offers a promising therapeutic strategy for PRL PitNETs.

Area of Science:

  • Molecular Biology
  • Oncology
  • Endocrinology

Background:

  • Epigenetics plays a crucial role in tumor progression and offers potential therapeutic targets.
  • Pituitary neuroendocrine tumors (PitNETs) are increasingly linked to epigenetic dysregulation.
  • The therapeutic potential of targeting epigenetic factors in PitNETs remains largely unexplored.

Purpose of the Study:

  • To investigate the involvement of the EZH2/H3K27me3 axis in the proliferation of lactotroph tumor cells.
  • To assess the EZH2/H3K27me3 axis as a potential therapeutic target for prolactin (PRL) PitNETs.

Main Methods:

  • Quantitative analysis of EZH2 and H3K27me3 levels in murine PRL tumors and control pituitaries.
  • Assessment of p21 mRNA levels and H3K27me3 enrichment at the p21 promoter in GH3 cells.
  • Inhibition of the EZH2/H3K27me3 axis in primary tumor cell cultures and GH3 cells.

Main Results:

  • Elevated EZH2 and H3K27me3 levels were observed in murine PRL tumors compared to controls.
  • Decreased p21 mRNA levels correlated with increased H3K27me3 enrichment in the promoter region of GH3 cells.
  • Targeted inhibition of the EZH2/H3K27me3 axis significantly reduced the proliferation of both primary tumor cells and GH3 cells.

Conclusions:

  • The EZH2/H3K27me3 axis is implicated in the proliferation of lactotroph tumor cells.
  • Inhibition of the EZH2/H3K27me3 axis demonstrates therapeutic potential for PRL PitNETs.
  • This axis represents an attractive therapeutic target for managing PRL PitNETs.
Keywords:
EZH2GSK343H3K27me3PRL tumor

More Related Videos

Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark10:09

Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark

Published on: January 26, 2018

7.6K
Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue08:12

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue

Published on: May 5, 2022

4.0K

Related Concept Videos

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...
3.1K
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...
4.6K
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...
3.8K
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K