Related Experiment Video

Updated: Jun 6, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

HER2 silences tumor suppression in breast cancer cells by switching expression of C/EBPß isoforms

Anna Arnal-Estapé1, Maria Tarragona, Mònica Morales

  • 1Oncology Programme, Institute for Research in Biomedicine, Barcelona, Spain.

Cancer Research
|November 25, 2010
PubMed

Insights

HER2-positive breast cancer cells evade tumor suppression by altering the C/EBPβ transcription factor. This switch, driven by HER2 signaling, blocks TGFβ and OIS pathways, promoting cancer growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Tumor progression involves overcoming tumor suppressor functions.
  • Transforming growth factor β (TGFβ) signaling and oncogene-induced senescence (OIS) are key tumor suppressors.
  • Mechanisms of suppressor function ablation in HER2-overexpressing breast cancer are unclear.

Purpose of the Study:

  • To investigate how HER2-overexpressing breast cancer cells evade TGFβ and OIS tumor suppression.
  • To identify the molecular players involved in this evasion mechanism.

Main Methods:

  • Analysis of C/EBPβ isoform expression in HER2-overexpressing breast cancer cells.
  • Investigating the role of CUGBP1 in regulating C/EBPβ isoforms.
  • Assessing the impact of LIP overexpression on TGFβ and OIS responses.
  • Evaluating the effect of trastuzumab treatment on LIP levels and suppressor functions.

Main Results:

  • HER2-overexpressing cells switch C/EBPβ isoform expression, favoring the inhibitory LIP isoform over the active LAP isoform.
  • HER2 signaling activates CUGBP1, promoting LIP production.
  • LIP overexpression disrupts LAP/Smad complex formation on the MYC promoter and impairs OIS activation.
  • Trastuzumab treatment reduces LIP levels, restoring TGFβ and OIS suppressor functions.

Conclusions:

  • HER2 signaling silences tumor suppressor functions through a novel mechanism involving C/EBPβ isoform switching.
  • This mechanism contributes to the aggressive nature of HER2-overexpressing breast cancer.
  • Targeting HER2 with therapies like trastuzumab can restore tumor suppressor functions.

More Related Videos

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material11:12

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Published on: August 1, 2018

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
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...
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...
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...