Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Esophageal keratinocyte invasion after loss of E-cadherin and TGF receptor type II


ABSTRACT: Esophageal cancer is one of the deadliest cancers as patients present at late stages of disease. Frequent gene alterations include the loss of E-cadherin and TGFb receptor type II. The goal of this study was to establish a model of esophageal cancer by introducing dominant-negative mutants of E-cadherin and TGFb receptor II. To analyze the functional consequences and gene expression chages induced by E-cadherin and TGFb receptor type II loss in esophageal cancer. Human esophageal keratinocytes were retrovirally transfected with wild-type full length E-cadherin, dominant-negative E-cadherin and dominant-negative TGFb receptor type II. Grown in organotypic cultures on a collagen/matrigel matrix with embedded fibroblast, the generated cell lines were analyzed for their potential to invade into the underlying matrix. Each cell lines was grown in duplicate in organotypic culture and therefore 2 replicates analyzed. Gene expression changes in invasive versus non-invasive areas were analyzed after RNA isolation using laser-capture microdissection resulting in 2 samples representing a normal esophageal epithelium (Ecad), 2 each of dominant-negative Ecad (Ecyto) non-invasive and invasive. To model the genetic alterations in esophageal cancer dominant-negative E-cadherin and dominant-negative TGFb receptor type II (Ecyto-dnTGFR) were expressed and 2 samples each, non-invasive and invasive, analyzed.

ORGANISM(S): Homo sapiens

SUBMITTER: Claudia Andl 

PROVIDER: E-GEOD-19472 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications


Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progr  ...[more]

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