Expression analysis of a subset of coregulators and three nuclear receptors in human colorectal carcinoma

Romina Giannini1, Aldo Cavallini

  • 1Laboratory of Biochemistry, National Institute for Digestive Diseases, I.R.C.C.S. Saverio de Bellis, 70013-Castellana Grotte, BA, Italy.

Anticancer Research
|November 29, 2005
PubMed

Insights

Estrogen receptor (ER) coactivators and corepressors show altered gene expression in colorectal tumors. ERbeta coactivator levels correlate with tumor development, suggesting a role in human colorectal carcinoma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Estrogen receptors (ERs) play a role in various cellular processes, including cancer development.
  • Coactivators and corepressors modulate ER activity and are implicated in tumorigenesis.
  • Understanding the expression patterns of ER-associated cofactors in colorectal cancer is crucial for elucidating disease mechanisms.

Purpose of the Study:

  • To investigate the gene expression profiles of ER-associated coactivators and corepressors in human colorectal tissues.
  • To determine the correlation between ER cofactors and colorectal tumor development.
  • To explore the potential role of ER cofactors in human colorectal carcinoma.

Main Methods:

  • Traditional Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to identify coactivator and corepressor gene expression.
  • Real-time PCR quantified mRNA levels of ER cofactors (ERalpha, ERbeta, ERRalpha) in matched tumor and normal colorectal tissues.
  • Statistical analysis examined correlations between cofactor gene expression and clinicopathological parameters.

Main Results:

  • Gene expression of coactivators generally decreased, while corepressors (NCoR, HDAC1, HDAC2, MTA1) increased from normal to tumor colorectal tissue.
  • REA, HDAC3, and MTA1L1 expression levels remained similar between normal and tumor tissues.
  • ERbeta gene expression correlated with p300, TIF-2, and REA in normal mucosa, and with REA in tumor tissue.

Conclusions:

  • Altered expression of ER-associated coactivators and corepressors is observed in colorectal cancer.
  • The co-induction of ERbeta and specific cofactors may be significant in human colorectal carcinoma development.
  • No association was found between ERalpha and coregulators or between coregulators and clinical parameters.

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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...