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Title: Transcription profiling of human HPV-immortalized keratinocytes      
dateReleased:
05-02-2009
description:
To identify early processes in carcinogenesis, we used an in vitro model, based on the initiating event in cervical cancer, human papillomavirus (HPV) transformation of keratinocytes. We compared gene expression in primary keratinocytes (K) and HPV16-transformed keratinocytes from early (E) and late (L) passages, and from benzo[a]pyrene treated L cells (BP). The transformed cells exhibit similar transcriptional changes to clinical cervical carcinoma. We revealed a contraction in expression of the apoptotic network during HF1 cell transformation, which affected the ability of L and BP cells to execute apoptosis, but did not lead to resistance to apoptotic stimuli. The contraction in the apoptotic machinery during the process of transformation was accompanied by a switch from apoptosis to necrosis in response to CDDP. The shrinkage of the pro- and anti-apoptotic networks appears to be part of a general contraction in the number of genes transcribed in L and BP cells. We also identified a large group of genes with induced expression, which are involved in cell metabolism and cell cycle, suggesting increased investment of the transformed cell in cellular proliferation. We hypothesize that the decrease in expression of many diverse pathways, including the pro- and anti-apoptotic networks, cuts the energy requirements for cell maintenance, allowing energy to be diverted towards rapid cell proliferation. This study supports the hypothesis that the process of cancer transformation may be accompanied by a shift from apoptosis to necrosis. Experiment Overall Design: We isolated mRNA from three independent cultures each of Keratinocytes and HPV16-immortalized keratinocytes : E, L and BP cells, grown under basal conditions. cDNA was prepared and hybridized to the Human Genome U133A Array (Affymetrix).
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-15156
refinement:
raw
alternateIdentifiers:
15156
dateSubmitted:
03-09-2009
keywords:
functional genomics
dateModified:
03-27-2012
creators:
Alexander Levitzki
availability:
available
types:
gene expression
name:
Homo sapiens
name:
unknown experiment type
ID:
A-AFFY-37
name:
Affymetrix GeneChip Human Genome U133A 2.0 [HG-U133A_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-15156/E-GEOD-15156.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-15156/E-GEOD-15156.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15156
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress