In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 69-69
Abstract:
Pancreatic cancer cells that have mesenchymal traits can be particularly migratory and resistant to chemotherapeutics. These cells are presumed to represent a more advanced and deadly population of cells relative to cancer cells with more differentiated, epithelial traits. The factors leading to the acquisition of a mesenchymal phenotype in pancreatic cancer are not well characterized. In this study, we tested the hypothesis that the development of a mesenchymal phenotype occurs selectively in tumor cells that harbor specific enabling genomic alterations. As a model system, we used pancreatic cancer cell lines that had either an epithelial-like or a mesenchymal-like phenotype when cultured in vitro, as defined by morphology and key molecular indicators. We used whole-genome comparative genomic hybridization to compare the genomic amplifications and deletions between 17 epithelial-like cell lines and 9 mesenchymal-like cell lines. An unbiased search revealed that 18 genes (each comprising at least three contiguous probes in a coding region) had alterations in a significantly greater percentage of the mesenchymal-like cells than the epithelial-like cells, whereas no genes had more frequent alterations in the epithelial-like cells. Sixteen of the 18 alterations were deletions, and 14 of the deletions were clustered in specific regions on chromosomes 8 and 9, suggesting the importance of those regions for suppressing de-differentiation. Some of the 18 genes were previously identified in studies of pancreatic cancer, such as SGCZ, KIAA1797 and SMAD4, while others were not. Certain genes showed a good correlation between DNA copy number and mRNA expression, providing evidence for the functional importance of those alterations. The known functions of the 18 genes include cell cycle control, cell membrane homeostasis, immune system regulation, and TGF-β pathway transduction, the deletion of which might provide improved survival advantage and cell structure modification required for metastasis. These findings support the concept that mesenchymal-like cancer cells are genetically more progressed than their epithelial-like counterparts and provide leads on the genomic hits that enable such progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 69. doi:1538-7445.AM2012-69
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-69
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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