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Pancreas. 2004 Nov;29(4):271-7.

The functional significance of the cholecystokinin-C (CCK-C) receptor in human pancreatic cancer.

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  • 1Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. jsmith2@psu.edu

Abstract

OBJECTIVES:

The aim of this study was to evaluate whether the CCK-C receptor, a splice variant of the CCK-B receptor, in human pancreatic cancer cells was associated with accelerated cancer cell growth.

METHODS:

In vitro, BxPC-3 cells were transfected with the antisense cDNA for the CCK-C receptor and growth of transfected cells was compared with that of wild-type (WT) and empty vector (EV)-transfected cells; expression was confirmed by RT-PCR and immunocytochemistry. In vivo, athymic nude mice bearing human BxPC-3 pancreatic cancers were treated for 28 days with either an antisense oligonucleotide specific to the CCK-C receptor, the same nucleotide sequence arranged in a scrambled fashion (nucleotide control), or vehicle (control).

RESULTS:

In culture, BxPC-3 cells transfected with the antisense cDNA for the CCK-C receptor were reduced in cell number 65% compared with WT and EV-transfected cell cultures at 6 days; this difference was statistically significant (P = 0.002). Transfected cells did not respond to exogenous gastrin with growth as did WT cells. Tumors of mice treated with the antisense oligonucleotide for CCK-C were 75% smaller in volume and 83% reduced in weight (P = 0.03) compared with the control tumors.

CONCLUSION:

These studies indicate that the CCK-C receptor is functional and plays a crucial role in growth of human pancreatic cancer.

PMID:
15502642
[PubMed - indexed for MEDLINE]
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