Related Experiment Video

Updated: Jun 2, 2026

Inducible and Reversible Dominant-negative (DN) Protein Inhibition
08:35

Inducible and Reversible Dominant-negative (DN) Protein Inhibition

Published on: January 7, 2019

Selective suppression of nuclear retinoic acid receptor beta gene expression in human pancreatic carcinomas

X Xu1, U Stier, S Rosewicz

  • 1UNIV TEXAS, MD ANDERSON CANC CTR, DEPT TUMOR BIOL, HOUSTON, TX 77030 USA. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT PATHOL, HOUSTON, TX 77030 USA. FREE UNIV BERLIN, KLINIKUM BENJAMIN FRANKLIN, DEPT INTERNAL MED, D-12200 BERLIN, GERMANY.

International Journal of Oncology
|May 6, 2011
PubMed

Insights

Retinoids show promise for pancreatic cancer treatment. However, reduced expression of the retinoic acid receptor-beta (RAR-beta) in malignant tissues may hinder retinoid therapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Expression Analysis

Background:

  • Retinoids are potential therapeutic agents for cancer due to their ability to restore normal cell growth and differentiation.
  • Nuclear retinoid receptors mediate the effects of retinoids on gene expression, making their assessment crucial for retinoid-based therapies.
  • Pancreatic cancer is a highly lethal malignancy with limited effective treatment options.

Purpose of the Study:

  • To investigate the expression of key nuclear retinoid receptors, specifically retinoic acid receptors (RARs) alpha, beta, and gamma, and retinoid X receptor (RXR) alpha, in human pancreatic carcinomas.
  • To compare the expression levels of these receptors in cancerous tissues versus adjacent normal pancreatic tissues.
  • To determine if altered expression of these receptors is associated with pancreatic cancer development or progression.

Main Methods:

  • In situ hybridization using digoxigenin-labeled antisense riboprobes was employed to detect mRNA transcripts for RAR-alpha, RAR-beta, RAR-gamma, and RXR-alpha.
  • Histological sections from 24 human pancreatic carcinomas and 20 adjacent normal pancreatic tissue specimens were analyzed.
  • Quantitative and qualitative assessment of receptor gene expression was performed.

Main Results:

  • All four retinoid receptors (RAR-alpha, RAR-beta, RAR-gamma, and RXR-alpha) were detected in adjacent normal pancreatic tissues.
  • RAR-alpha, RAR-gamma, and RXR-alpha were detected in all analyzed pancreatic carcinoma specimens.
  • RAR-beta mRNA transcripts were found in only 67% of malignant tissues, with significantly lower expression levels compared to normal tissues, particularly in moderately and poorly differentiated cancers.

Conclusions:

  • Selective decrease or loss of RAR-beta gene expression is observed in a subset of pancreatic carcinomas.
  • The diminished expression of RAR-beta in pancreatic cancer tissues suggests a potential role in the development or progression of the disease.
  • These findings highlight the importance of assessing RAR-beta expression for evaluating the potential efficacy of retinoid-based therapies in pancreatic cancer.

More Related Videos

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells09:45

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells

Published on: May 21, 2019

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
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...
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:
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...