Transcriptomics

Dataset Information

3

Gene expression profiles (stroma and epithelium) of prostate cancer mouse models (JOCK1, Pro-Cat × JOCK1, Ubi-Cat × JOCK1)


ABSTRACT: The fibroblast growth factor receptor (FGFR) and canonical Wnt signaling pathways are important regulators of carcinogenesis; however, the interaction between these two pathways in the context of prostate cancer (PCa) has not been fully elucidated. Using novel transgenic mouse models, we describe Wnt-induced synergistic acceleration of FGFR1-driven adenocarcinoma; largely due to pronounced fibroblastic reactive stroma (RS) activation surrounding prostatic intraepithelial neoplasia (PIN) lesions in endogenous and reconstitution assays. Finally, both mouse and human RS are characterized by increases in TGF-β signaling heterogeneity immediately adjacent to PIN lesions; however, heterogeneity is lost during later stages of progression, likely contributing to tissue invasion. These studies confirm the importance of the FGFR1-Wnt-TGF-β signaling axes as driving forces behind reactive stroma and aggressive adenocarcinoma. To elucidate the mechanism behind the Wnt-accelerated FGFR1 adenocarcinoma, we performed laser capture microdissection (LCM) to separate pre-cancerous (hyperplasia and PIN) epithelia and adjacent reactive-stroma cells. We utilized frozen samples from specific time points (JOCK1, 40 weeks, Pro-Cat × JOCK1 and Ubi-Cat × JOCK1, 24 weeks) and performed gene expression profiling on the respective tissues.

ORGANISM(S): Mus musculus  

SUBMITTER: David Spencer   Chad Creighton  David Rowley  Julienne Carstens 

PROVIDER: E-GEOD-41344 | ArrayExpress | 2014-01-07

SECONDARY ACCESSION(S): GSE41344PRJNA176665

REPOSITORIES: GEO, ArrayExpress

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Publications


The reactive stroma surrounding tumor lesions performs critical roles ranging from supporting tumor cell proliferation to inducing tumorigenesis and metastasis. Therefore, it is critical to understand the cellular components and signaling control mechanisms that underlie the etiology of reactive stroma. Previous studies have individually implicated fibroblast growth factor receptor 1 (FGFR1) and canonical WNT/β-catenin signaling in prostate cancer progression and the initiation and maintenance o  ...[more]

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