Journal article
Overexpression of membrane proteins in primary and metastatic gastrointestinal neuroendocrine tumors
Annals of surgical oncology, Vol.20 Suppl 3(S3), pp.S739-746
12/2013
DOI: 10.1245/s10434-013-3318-6
PMCID: PMC3981744
PMID: 24114056
Abstract
Small bowel and pancreatic neuroendocrine tumors (SBNETs and PNETs) are rare tumors whose incidence is increasing. Drugs targeting the somatostatin receptor are beneficial in these tumors. To identify additional cell-surface targets, we recently found receptors and membrane proteins with gene expression significantly different from adjacent normal tissues in a small number of primary SBNETs and PNETs. We set out to validate these expression differences in a large group of primary neuroendocrine tumors and to determine whether they are present in corresponding liver and lymph node metastases.
Primary SBNETs and PNETs, normal tissue, nodal, and liver metastases were collected and mRNA expression of six target genes was determined by quantitative PCR. Expression was normalized to GAPDH and POLR2A internal controls, and differences as compared to normal tissue were assessed by Welch's t test.
Gene expression was determined in 45 primary PNETs with 20 nodal and 17 liver metastases, and 51 SBNETs with 50 nodal and 29 liver metastases. Compared to normal tissue, the oxytocin receptor (OXTR) showed significant overexpression in both primary and metastatic SBNETs and PNETs. Significant overexpression was observed for MUC13 and MEP1B in PNET primary tumors, and for GPR113 in primary SBNETs and their metastases. SCTR and ADORA1 were significantly underexpressed in PNETs and their metastases. OXTR protein expression was confirmed by immunohistochemistry.
OXTR is significantly overexpressed relative to normal tissue in primary SBNETs and PNETs, and this overexpression is present in their liver and lymph node metastases, making OXTR a promising target for imaging and therapeutic interventions.
Details
- Title: Subtitle
- Overexpression of membrane proteins in primary and metastatic gastrointestinal neuroendocrine tumors
- Creators
- Jennifer C Carr - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IAScott K Sherman - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IADonghong Wang - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IAFadi S Dahdaleh - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IAAndrew M Bellizzi - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IAM Sue O'Dorisio - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IAThomas M O'Dorisio - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IAJames R Howe - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Annals of surgical oncology, Vol.20 Suppl 3(S3), pp.S739-746
- DOI
- 10.1245/s10434-013-3318-6
- PMID
- 24114056
- PMCID
- PMC3981744
- NLM abbreviation
- Ann Surg Oncol
- ISSN
- 1068-9265
- eISSN
- 1534-4681
- Publisher
- Springer Science and Business Media LLC; United States
- Grant note
- R01 CA167632 / NCI NIH HHS 5T32-CA148062-03 / NCI NIH HHS T32 CA148062 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 12/2013
- Academic Unit
- Stead Family Department of Pediatrics; Pathology; Surgery; Endocrinology and Metabolism; Otolaryngology; Internal Medicine
- Record Identifier
- 9984047734502771
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