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E-GEOD-26966 - Transcription profiling by array of human gonadotrope and null cell pituitary tumors

Status
Released on 31 January 2011, last updated on 12 August 2015
Organism
Homo sapiens
Samples (23)
Array (1)
Protocols (7)
Description
Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism, together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options. To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples. Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45β, GADD45γ and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1. PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45β was performed. Overexpression of GADD45β in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45γ, methylation interference assays showed no evidence of epigenetic modification of the GADD45β promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45β is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45γ, GADD45β is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression. To elucidate mechanisms involved in pituitary tumorigenesis and progression, we performed individual gene expression microarray analysis using Affy U133 Plus 2.0 GeneChips comparing 14 gonadotrope tumors with 9 normal pituitary samples obtained at autopsy.
Experiment type
transcription profiling by array 
Contacts
Michael Edwards <michael.edwards@ucdenver.edu>, Aaron J Knox, Katherine A Michaelis, Margaret E Wierman, Mei Xu, Michael G Edwards
Citation
Identification of growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a novel tumor suppressor in pituitary gonadotrope tumors. Michaelis KA, Knox AJ, Xu M, Kiseljak-Vassiliades K, Edwards MG, Geraci M, Kleinschmidt-DeMasters BK, Lillehei KO, Wierman ME.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-26966.idf.txt
Sample and data relationshipE-GEOD-26966.sdrf.txt
Raw data (1)E-GEOD-26966.raw.1.zip
Processed data (1)E-GEOD-26966.processed.1.zip
Array designA-AFFY-44.adf.txt
Links