Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia

Segara, D., Biankin, A. V., Kench, J. G., Langusch, C. C., Dawson, L. C., Skalicky, D. A., Gotley, D. C., Coleman, M. J., Sutherland, R. L. and Henshall, S. M. (2005) Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia. Clinical Cancer Research, 11 9: 3587-3596. doi:10.1158/1078-0432.CCR-04-1813


Author Segara, D.
Biankin, A. V.
Kench, J. G.
Langusch, C. C.
Dawson, L. C.
Skalicky, D. A.
Gotley, D. C.
Coleman, M. J.
Sutherland, R. L.
Henshall, S. M.
Title Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
Publication date 2005
Sub-type Article (original research)
DOI 10.1158/1078-0432.CCR-04-1813
Volume 11
Issue 9
Start page 3587
End page 3596
Total pages 10
Editor J. Mendelsohn
Place of publication USA
Publisher American Association for Cancer Research
Collection year 2005
Language eng
Subject C1
321015 Oncology and Carcinogenesis
730108 Cancer and related disorders
Abstract Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and Pan IN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early Pan IN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. Conclusions: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.
Keyword Oncology
Acute Promyelocytic Leukemia
Gene-expression
Induced Differentiation
Lineage Selection
Epithelial-cells
Responsive Gene
Homeobox Genes
Duct Lesions
Adenocarcinoma
Growth
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2006 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 06:45:31 EST