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Series GSE15299 Query DataSets for GSE15299
Status Public on Jun 02, 2009
Title Modeling Inducible Human Tissue Neoplasia Identifies an ECM Interaction Network Involved in Cancer Progression
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Summary To elucidate mechanisms of cancer progression, we generated inducible human neoplasia in 3-dimensionally intact epithelial tissue. Gene expression profiling of both epithelia and stroma at specific time points during tumor progression revealed sequential enrichment of genes mediating discrete biologic functions in each tissue compartment. A core cancer progression signature was distilled using the increased signaling specificity of downstream oncogene effectors and subjected to network modeling. Network topology predicted that tumor development depends upon specific ECM-interacting network hubs. Blockade of one such hub, the b1 integrin subunit, disrupted network gene expression and attenuated tumorigenesis in vivo. Thus, integrating network modeling and temporal gene expression analysis of inducible human neoplasia provides an approach to prioritize and characterize genes functioning in cancer progression.
Overall design There are 3 experiments in this study: (1a) a time course of human epidermal tissue transformed by oncogenic ER:H-Ras and IkBaM comprising days 0, 5, 20, and 35 post Ras activation using 4OHT; (1b) a matched time course of adjacent mouse stromal tissue during tumor progression; (2) Arrays comparing 4OHT-induced, Raf-1:ER/IkBaM transformed epidermal tissue and -4OHT controls; and (3) Arrays comparing Ras:ER/IkBaM grafts co-treated with 4OHT and either IgG control antibody or an anti-b1 integrin blocking antibody, P5D2 for 30 days. All arrays were done in biologic duplicate.

Epidermal tissue co-expressing ER:H-RasG12V (ER:Ras) and IkBaM was regenerated on female scid/scid mouse recipients. Grafts were allowed to heal for at least 3 weeks before Ras activation via daily i.p. injections of 730ug of 4OHT (in 110ul of a corn oil/ethanol mixture). Duplicate grafts were harvested after 0, 5, 20, and 35 days of 4OHT treatment. Laser capture microdissection was utilized to independently isolate epithelial cells of the basal most layers and adajacent stromal tissue for each time point. RNA was subjected to one round of T7-based linear amplification (Ambion Message Amp II enhanced kit) and hybridized to either HG-U133A 2.0 or MG-430A affymetrix oligonucleotide arrays. Arrays from this experiment are labeled Ras and Stroma, respectively. The second experment was performed on Raf-1:ER/IkBaM expressing grafts with and without 4OHT treament for 30 days. The third experiment was done comparing ER:Ras/IkBaM grafts concomitantly treated with 4OHT and 1.5mg/week of either IgG control antibody or a mouse monoclonal blocking antibody against b1 integrin for 30 days. For experiments 2 and 3, HG-U133A 2.0 GeneChips were used; 4OHT treatment and RNA isolation/amplification was performed as above.
Contributor(s) Reuter JA
Citation(s) 19477427
Submission date Mar 19, 2009
Last update date Dec 06, 2018
Contact name Paul A Khavari
Organization name Stanford University
Department Dermatology
Lab Khavari Lab
Street address 259 Campus Dr
City Stanford
State/province CA
ZIP/Postal code 94305-5168
Country USA
Platforms (2)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
GPL8321 [Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array
Samples (24)
GSM382366 Epidermis_Ras_0 Days 4OHT_rep1
GSM382367 Epidermis_Ras_0 Days 4OHT_rep2
GSM382368 Epidermis_Ras_5 Days 4OHT_rep1
BioProject PRJNA115827

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE15299_RAW.tar 44.5 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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