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CCK(2) receptor splice variant with intron 4 retention in human gastrointestinal and lung tumours

Meike Körner1, Beatrice Waser, Jean Claude Reubi

  • 1Mayo Clinic, Cancer Center and Department of Molecular Pharmacology and Experimental Therapeutics, Scottsdale, Arizona, USA. meike.koerner@pathology.unibe.ch

Journal of Cellular and Molecular Medicine
|July 25, 2009
PubMed

Insights

The cholecystokinin type 2 receptor splice variant (CCK2Ri4sv) is a novel marker found in specific gastrointestinal and lung tumors. Its high incidence in small cell lung cancer and GIST suggests it could be a valuable clinical target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • The cholecystokinin type 2 (CCK2) receptor is present in various gastrointestinal and lung tumors.
  • A splice variant, CCK2Ri4sv, exhibits constitutive activity and is linked to tumor growth.
  • The clinical significance of CCK2Ri4sv necessitates quantitative characterization across diverse tumor types.

Purpose of the Study:

  • To quantitatively assess the occurrence of the CCK2Ri4sv splice variant in a wide range of gastrointestinal and lung tumors.
  • To compare the expression of CCK2Ri4sv with wild-type CCK2 receptor in tumor tissues and normal counterparts.
  • To evaluate the potential of CCK2Ri4sv as a specific biomarker and clinical target for certain cancers.

Main Methods:

  • RT-PCR (real-time and end-point) was used to measure CCK2 receptor and CCK2Ri4sv transcript expression.
  • In vitro receptor autoradiography assessed total CCK2 receptor protein expression.
  • A comprehensive panel of 81 gastrointestinal and lung tumors and 21 normal tissues were analyzed.

Main Results:

  • Wild-type CCK2 receptor transcripts were ubiquitously detected in most tumors and normal tissues.
  • CCK2Ri4sv mRNA was predominantly found in insulinomas (100%), GIST (100%), and SCLC (67%).
  • CCK2Ri4sv expression was rare in pancreatic, colorectal, gastric carcinomas, and non-SCLC, and absent in normal tissues.

Conclusions:

  • The CCK2Ri4sv splice variant serves as a specific marker for certain gastrointestinal and lung tumors.
  • Its high incidence and selectivity in SCLC and GIST position it as a promising clinical target.
  • Further research into CCK2Ri4sv could lead to targeted therapeutic strategies for these specific cancers.

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