Related Experiment Video

Updated: May 28, 2026

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

Characterization of a novel five-transmembrane domain cholecystokinin-2 receptor splice variant identified in human

Claire Sanchez1, Chantal Escrieut, Pascal Clerc

  • 1Université de Toulouse 3, EA 4552 Toulouse, France.

Molecular and Cellular Endocrinology
|November 2, 2011
PubMed

Insights

A novel cholecystokinin-2 receptor (CCK2R) splice variant was discovered in various tumors. This variant reduces CCK2R on cell membranes, impacting tumor progression and CCK2R-targeting therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The cholecystokinin-2 receptor (CCK2R) is implicated in cancer progression and is a target for radiolabeled ligands.
  • Discrepancies between CCK2R mRNA levels and receptor binding sites suggest the presence of non-functional variants.

Purpose of the Study:

  • To investigate abnormally spliced CCK2R variants in tumors known to express CCK2R.
  • To characterize the functional impact of a novel CCK2R splice variant on receptor expression and activity.

Main Methods:

  • Screening of tumor samples (medullary thyroid carcinomas, GISTs, leiomyomas, leiomyosarcomas, gastroenteropancreatic tumors) for CCK2R splice variants.
  • Cloning and ectopic expression of a novel CCK2R variant in COS-7 cells.
  • Assessment of CCK2R membrane density and CCK2R-mediated signaling (PLC, ERK activation) upon co-expression with the variant.

Main Results:

  • A novel CCK2R splice variant encoding a putative five-transmembrane domain receptor was identified, comprising up to 6% of total CCK2R.
  • This variant is biologically inactive and retained in the endoplasmic reticulum.
  • Co-expression of the variant with wild-type CCK2R reduced CCK2R membrane expression and attenuated CCK2R-mediated signaling.

Conclusions:

  • A novel CCK2R splice variant acts as a dominant-negative regulator of CCK2R membrane density and function.
  • This variant may play a role in tumor pathophysiology and influence the efficacy of in vivo CCK2R-targeting strategies.

More Related Videos

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

Identification of Functional Protein Regions Through Chimeric Protein Construction11:39

Identification of Functional Protein Regions Through Chimeric Protein Construction

Published on: January 8, 2019

Related Concept Videos

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...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
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...
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview