Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Primary and ras keratinocytes plus TGFbeta1

ABSTRACT: We have compared the response to TGFbeta1 in normal and v-rasHa transduced primary mouse keratinocytes using NCI cDNA microarrays. This analysis reveals that Ha-ras alters global TGFbeta1 mediated gene expression in a gene specific manner. The expression pattern of TGFbeta1 immediate early response genes and down regulation of cell cycle control genes is not altered by Ha-ras but the induction of most extracellular matrix genes is blocked. Using Smad3 null keratinocytes, we find that the majority of TGFbeta1 responsive genes in primary keratinocytes are Smad3 dependent, but patterns of transcriptional responses suggest that the ability of Ha-ras to block TGFbeta1 mediated gene expression is not dependent on Smad3. However, the combination of oncogenic ras and loss of Smad3 prevents the TGFbeta1 dependent suppression of genes associated with cell cycle progression and apoptosis observed with either genotype alone. In addition several extracellular matrix genes are super-repressed by TGFbeta1 in the Ha-ras Smad3 null keratinocytes. These data provide a genomic framework for understanding how disruptions of TGFbeta signaling and oncogenic ras cooperate to promote premalignant progression of primary keratinocytes. Keywords: time series design RNA from Balb/c primary and ras keratinocytes treated for 1, 6, 24, and 48 hours with TGFbeta1 at 1ng/ml was compared to RNA from the corresponding untreated controls. For each timepoint sample from primary and ras cells, multiple arrays (including dye swaps) were analyzed. There are 6, 7, 6, and 5 arrays analyzed for RNA from primary keratinocytes treated for 1, 6, 24, and 48 hours as compared to RNA from untreated primary cells, respectively. There are 6, 8, 7, and 5 arrays analyzed for RNA from ras keratinocytes treated for 1, 6, 24, and 48 hours as compared to RNA from untreated ras cells, respectively. There are 50 arrays analyzed for the Balb/c time-course dataset. RNA from Smad3 WT and KO primary and ras keratinocytes treated 48 hours with TGFbeta1 were compared to RNA from its untreated corresponding controls. There are 6 arrays analyzed for the Smad3 WT/KO data set. There are 56 arrays in this series.

ORGANISM(S): Mus musculus

SUBMITTER: DONG-SOON BAE

PROVIDER: E-GEOD-3228 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tumor suppressor and oncogene actions of TGFbeta1 occur early in skin carcinogenesis and are mediated by Smad3.

Bae Dong-Soon DS Blazanin Nicholas N Licata Mathew M Lee Jessica J Glick Adam B AB

Molecular carcinogenesis 20090501 5

Interactions between TGFbeta1 and ras signaling pathways play an important role in cancer development. Here we show that in primary mouse keratinocytes, v-ras(Ha) does not block the early biochemical events of TGFbeta1 signal transduction but does alter global TGFbeta1 mediated gene expression in a gene specific manner. Expression of Smad3 dependent TGFbeta1 early response genes and the TGFbeta1 cytostatic gene expression response were not altered by v-ras(Ha) consistent with an intact TGFbeta1 ...[more]

PMID: 18942075

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Dataset Information

Primary and ras keratinocytes plus TGFbeta1

Publications

Tumor suppressor and oncogene actions of TGFbeta1 occur early in skin carcinogenesis and are mediated by Smad3.

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