Disrupting ß-catenin dependent Wnt signaling activates an invasive gene program predictive of colon cancer progression
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ABSTRACT:
PROVIDER: PRJNA534423 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8948910_1.fastq.gz | Fastqsanger.gz | |||
| SRR8948910_2.fastq.gz | Fastqsanger.gz | |||
| SRR8948920_1.fastq.gz | Fastqsanger.gz | |||
| SRR8948920_2.fastq.gz | Fastqsanger.gz | |||
| SRR8948901_1.fastq.gz | Fastqsanger.gz |
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Project description:Focal nodular hyperplasias (FNHs) are benign liver lesions considered to be a hyperplastic response to increased blood flow in otherwise normal liver. In contrast, FNH-like nodules occur in cirrhotic liver but share similar histopathological features. To better understand the pathophysiology of FNH, we performed a transcriptomic analysis. Methods: Affymetrix and cDNA microarrays were used to compare gene expression in eight FNHs with that in tissue from six normal livers. Selected genes were validated with quantitative RT-PCR in 70 benign liver tumors including adenomas and cirrhotic and FNH-like lesions. Results: Among the deregulated genes in FNHs, 19 were physiologically zonated in the normal liver lobule. All six periveinous genes were up-regulated in FNH, whereas 13 genes normally expressed in the periportal area were down-regulated. Immunohistochemistry revealed that glutamine synthetase was markedly overexpressed, forming anastomosed areas usually centered on visible veins. ß-catenin mRNA was slightly but significantly overexpressed, as were several known ß-catenin target genes. Moreover, activated hypophosphorylated ß-catenin protein accumulated in FNH in the absence of activating mutations. These results suggest zonated activation of the ß-catenin pathway specifically in FNH, whereas the other benign hepatocellular tumors, including FNH-like lesions, demonstrated an entirely different pattern of ß-catenin expression. Conclusions: In FNH, increased expression of the ß-catenin pathway was restricted to enlarged periveinous areas, which may explain the slight polyclonal over-proliferation of hepatocytes at the origin of the lesion. FNH-like nodules may have a different pathogenetic origin. Keywords: Disease state analysis
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