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

Sanchez, Claire; Escrieut, Chantal; Clerc, Pascal; Gigoux, Véronique; Waser, Beatrice; Reubi, Jean-Claude; Fourmy, Daniel (2012). Characterization of a novel five-transmembrane domain cholecystokinin-2 receptor splice variant identified in human tumors. Molecular and cellular endocrinology, 349(2), pp. 170-9. Shannon: Elsevier Ireland 10.1016/j.mce.2011.10.010

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The cholecystokinin-2 receptor (CCK2R), is expressed in cancers where it contributes to tumor progression. The CCK2R is over-expressed in a sub-set of tumors, allowing its use in tumor targeting with a radiolabel ligand. Since discrepancies between mRNA levels and CCK2R binding sites were noticed, we searched for abnormally spliced variants in tumors from various origins having been previously reported to frequently express cholecystokinin receptors, such as medullary thyroid carcinomas, gastrointestinal stromal tumors, leiomyomas and leiomyosarcomas, and gastroenteropancreatic tumors. A variant of the CCK2R coding for a putative five-transmembrane domains receptor has been cloned. This variant represented as much as 6% of CCK2R levels. Ectopic expression in COS-7 cells revealed that this variant lacks biological activity due to its sequestration in endoplasmic reticulum. When co-expressed with the CCK2R, this variant diminished membrane density of the CCK2R and CCK2R-mediated activity (phospholipase-C and ERK activation). In conclusion, a novel splice variant acting as a dominant negative on membrane density of the CCK2R may be of importance for the pathophysiology of certain tumors and for their in vivo CCK2R-targeting.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Waser, Beatrice and Reubi-Kattenbusch, Jean-Claude

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0303-7207

Publisher:

Elsevier Ireland

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:18

Last Modified:

14 Oct 2019 15:40

Publisher DOI:

10.1016/j.mce.2011.10.010

PubMed ID:

22040601

Web of Science ID:

000300480100008

URI:

https://boris.unibe.ch/id/eprint/5550 (FactScience: 210303)

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