CCK2 receptor splice variant with intron 4 retention in human gastrointestinal and lung tumours

Körner, Meike; Waser, Beatrice; Reubi, Jean-Claude; Miller, Laurence J. (2010). CCK2 receptor splice variant with intron 4 retention in human gastrointestinal and lung tumours. Journal of Cellular and Molecular Medicine, 14(4), pp. 933-943. Bucharest (Romania): Wiley 10.1111/j.1582-4934.2009.00859.x

[img]
Preview
Text
16.pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (1MB) | Preview
[img]
Preview
Text
j.1582-4934.2009.00859.x.pdf - Published Version
Available under License Publisher holds Copyright.

Download (25MB) | Preview

The wild-type cholecystokinin type 2 (CCK(2)) receptor is expressed in many gastrointestinal and lung tumours. A splice variant of the CCK(2) receptor with retention of intron 4 (CCK(2)Ri4sv) showing constitutive activity associated with increased tumour growth was described in few colorectal, pancreatic and gastric cancers. Given the potential functional and clinical importance of this spliceoform, its occurrence was quantitatively characterized in a broad collection of 81 gastrointestinal and lung tumours, including insulinomas, ileal carcinoids, gastrointestinal stromal tumours (GIST), gastric, colorectal and pancreatic ductal adenocarcinomas, cholangiocellular and hepatocellular carcinomas, small cell lung cancers (SCLC), non-SCLC (nSCLC) and bronchopulmonary carcinoids, as well as 21 samples of corresponding normal tissues. These samples were assessed for transcript expression of total CCK(2) receptor, wild-type CCK(2) receptor and CCK(2)Ri4sv with end-point and real-time RT-PCR, and for total CCK(2) receptor protein expression on the basis of receptor binding with in vitro receptor autoradiography. Wild-type CCK(2) receptor transcripts were found in the vast majority of tumours and normal tissues. CCK(2)Ri4sv mRNA expression was present predominantly in insulinomas (incidence 100%), GIST (100%) and SCLC (67%), but rarely in pancreatic, colorectal and gastric carcinomas and nSCLC. It was not found in wild-type CCK(2) receptor negative tumours or any normal tissues tested. CCK(2)Ri4sv transcript levels in individual tumours were low, ranging from 0.02% to 0.14% of total CCK(2) receptor transcripts. In conclusion, the CCK(2)Ri4sv is a marker of specific gastrointestinal and lung tumours. With its high selectivity for and high incidence in SCLC and GIST, it may represent an attractive clinical target.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Körner Jachertz, Meike; Waser, Beatrice and Reubi-Kattenbusch, Jean-Claude

Subjects:

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

ISSN:

1582-1838

Publisher:

Wiley

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:07

Last Modified:

28 Apr 2020 15:57

Publisher DOI:

10.1111/j.1582-4934.2009.00859.x

PubMed ID:

19627395

Web of Science ID:

000277526400018

BORIS DOI:

10.7892/boris.16

URI:

https://boris.unibe.ch/id/eprint/16 (FactScience: 165572)

Actions (login required)

Edit item Edit item
Provide Feedback