Related Experiment Video

Updated: Dec 17, 2025

The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior
08:12

The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior

Published on: June 12, 2019

5.4K

The GATA3 X308_Splice breast cancer mutation is a hormone context-dependent oncogenic driver

Natascha Hruschka1, Mark Kalisz2, Maria Subijana1

  • 1Institute of Cancer Research, Medical University Vienna, Comprehensive Cancer Center, Vienna, Austria.

Oncogene
|June 27, 2020
PubMed

Insights

New GATA3 mutations create a "neoGATA3" neoprotein, impacting estrogen receptor (ER) signaling in breast cancer. This finding highlights the need for functional analysis of cancer drivers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oncogenic driver mutations are diverse and require functional classification.
  • GATA3 mutations exemplify this, with specific alterations leading to a distinct neoprotein.

Purpose of the Study:

  • To investigate the function of a novel GATA3 neoprotein, termed "neoGATA3," arising from common mutations.
  • To analyze the impact of neoGATA3 on estrogen receptor (ER)-dependent gene expression in breast cancer.

Main Methods:

  • Analysis of molecular data from over 3000 breast cancer patients.
  • In vitro mechanistic studies.
  • Chromatin immunoprecipitation sequencing (ChIP-Seq) to assess ER binding.

Main Results:

  • neoGATA3-generating mutations dysregulate ER-dependent transcription in breast cancer.
  • neoGATA3 interferes with estrogen and progesterone receptor transcriptional programs.
  • Reduced ER binding, particularly at distal regions, was observed in neoGATA3-expressing cells, affecting gene expression fine-tuning.

Conclusions:

  • neoGATA3 exhibits context-dependent proliferative effects based on the estrogen/progesterone ratio.
  • Functional characterization of cancer driver mutations is crucial for clinical applications.

More Related Videos

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

23.8K
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

6.7K

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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...
10.9K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.9K
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...
9.3K
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...
7.6K
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...
5.0K
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...
5.7K