Unknown,Transcriptomics,Genomics,Proteomics

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EMT is the dominant program in human colon cancer (lung)

ABSTRACT: mRNA profiling of 93 lung cancer cell lines supporting data for PMID: 21251323 93 lung cancer cell lines profiled at baseline

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Nebozhyn

PROVIDER: E-GEOD-28709 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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EMT is the dominant program in human colon cancer.

Loboda Andre A Nebozhyn Michael V MV Watters James W JW Buser Carolyne A CA Shaw Peter Martin PM Huang Pearl S PS Van't Veer Laura L Tollenaar Rob A E M RA Jackson David B DB Agrawal Deepak D Dai Hongyue H Yeatman Timothy J TJ

BMC medical genomics 20110120

<h4>Background</h4>Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging.<h4>Methods</h4>We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1) of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence.<h4>Results</h4>Here we r ...[more]

PMID: 21251323

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Project description:Deregulated developmental processes in the cerebellum cause medulloblastoma, the most common malignant tumor of the central nervous system. About 20-30% of cases are caused by mutations increasing the activity of the Sonic hedgehog (Shh) pathway, a critical mitogen in cerebellar development. The proto-oncogene Smoothened is a key transducer of the Shh pathway. Activating mutations in Smoothened that lead to constitutive activity of the Shh pathway have been identified in human medulloblastoma. To understand the molecular and cellular effects of Smoothened variants in normal development and medulloblastoma genesis, we generated the SmoA2 transgenic mouse model which expresses the transgene exclusively in granule neuron precursors. In this study, we demonstrate how two point mutations in a single molecule can produce starkly different phenotypes as seen in comparison to our previous model, ND2:SmoA1. The SmoA2 mice have severe aberrations in cerebellar development whereas the SmoA1 mice are largely normal during development. Medulloblastomas in the SmoA2 mice develop in the dysplastic cerebellar milieu. Intriguingly, despite disruptions in the stereotypic organization of the cerebellum, the SmoA2 mice do not exhibit any overt abnormalities in motor coordination. The differences in the global transcriptional profiles downstream of SmoA1 and SmoA2 further demonstrate the distinctiveness of the two oncogenic Smoothened mutations. The SmoA2 model serves as a unique spatiotemporal tool to investigate the functional significance of the reiterative cerebellar circuitry as well as to further understand Shh pathway mechanics in cerebellar development and oncogenesis. We previously generated a SmoA1 transgenic mouse medulloblastoma model, which expresses the SmoA1 transgene driven by the GNP-specific fragment of the promoter of ND2 transcription factor leading to constitutively active Shh signaling exclusively in the cerebellum. In this study, we characterize the ND2:SmoA2 transgenic mouse model with a similarly designed transgene expressing the SmoA2 mutation. To assess transcriptional changes downstream of SmoA1 and SmoA2, we evaluated global gene expression profiles of P5 SmoA1, SmoA2 and Wt age-matched cerebella. We chose this specific developmental stage because (1) the phenotypes of SmoA1 and SmoA2 are robust and distinct at P5; (2) at P5 GNPs undergo proliferation, migration and differentiation and therefore expression profiling could capture key differences in multiple processes.

Dataset Information

EMT is the dominant program in human colon cancer (lung)

Publications

EMT is the dominant program in human colon cancer.

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