KLF4 is a novel candidate tumor suppressor gene in pancreatic ductal carcinoma Journal Article
| Authors: | Zammarchi, F.; Morelli, M.; Menicagli, M.; Di Cristofano, C.; Zavaglia, K.; Paolucci, A.; Campani, D.; Aretini, P.; Boggi, U.; Mosca, F.; Cavazzana, A.; Cartegni, L.; Bevilacqua, G.; Mazzanti, C. M. |
| Article Title: | KLF4 is a novel candidate tumor suppressor gene in pancreatic ductal carcinoma |
| Abstract: | Ductal pancreatic carcinoma (DPC) is a deadly disease with an incidence of 9 cases in 100,000 people per year and a mortality rate close to 100%. Allelic losses in the long arm of chromosome 9 are commonly encountered in many human malignancies but no data are yet available about DPC. We screened 40 laser-microdissected DPC samples and 6 pre-invasive lesions for 9 microsatellite mapping markers of region 9q21.3 through 9q34.2. A small overlapping region of deletion, spanning 8 million base pairs, was identified between D9S127 and D9S105. Two genes, RSG3 and KLF4, mapped to 9q31.1 through 9q32, were further investigated. A highly significant association was found between KLF4 gene expression levels and genomic status. Similarly, absence of immunohistochemical expression of KLF4 protein was found in 86.8% cases of DPC (33/ 38). Overexpression of KLF4 in a human pancreatic carcinoma cell line induced a significant decrease in the proliferation associated with up-regulation of p21 and the down-regulation of cyclin D1. In conclusion, we identified a novel oncosuppressor region located at the 9q 31.1-3 locus that is lost in DPC at high frequency. Loss of KLF4 expression is closely related to the genomic loss, and its restoration inhibits cancer cell proliferation, suggesting a key suppressor role in pancreatic tumorigenesis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
| Keywords: | immunohistochemistry; controlled study; human tissue; protein expression; human cell; promoter region; gene deletion; gene expression; genetic association; pancreas carcinoma; gene mapping; tumor suppressor gene; down regulation; microsatellite marker; heterozygosity loss; cyclin d1; protein p21; carcinoma cell; kruppel like factor 4; chromosome 9q; laser microdissection |
| Journal Title: | American Journal of Pathology |
| Volume: | 178 |
| Issue: | 1 |
| ISSN: | 0002-9440 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2011-01-01 |
| Start Page: | 361 |
| End Page: | 372 |
| Language: | English |
| DOI: | 10.1016/j.ajpath.2010.11.021 |
| PROVIDER: | scopus |
| PMCID: | PMC3069861 |
| PUBMED: | 21224073 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: AJPAA" - "Source: Scopus" |
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