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A mutation in the c-Fos gene associated with congenital generalized lipodystrophy

ABSTRACT: Lipodystrophies resemble syndromes of disturbed adipocyte biology or development and severe congenital forms (CGL) lack adipose tissue. The ubiquitous immediate-early gene c-fos is one essential transcription factor to initiate adipocyte differentiation. In a CGL patient we identified a single homozygous point mutation in the promoter of c-fos gene. The mutation facilitates the formation of a novel specific protein/ DNA complex and ubiquitously reduces basal and inducible c-fos transcription activity. We used microarrays to determine differences in gene expression due to a repressive c-fos promoter mutation in a patient with CGL. Cultued fibroblasts of non diabetic controls and a patient with c-fos promoter mutation were analyzed at identical passage number and growth conditions without further additional treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Birgit Knebel

PROVIDER: E-GEOD-39825 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Analyses of a deactivation genetic variation in Ha-Ras proto oncogene identified in a patient wit premature aging and insulin resistance

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2013-08-07 | E-GEOD-49566 | biostudies-arrayexpress

A mutation in the c-Fos gene associated with congenital generalized lipodystrophy

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Identification of candidate genes involved in fructooligosaccharides (FOS) utilization by Lactobacillus paracasei

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Genome-wide mapping of Fos binding site (K562)

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2009-12-31 | E-GEOD-19546 | biostudies-arrayexpress

Expression analyses of inducible c-Fos expressing kerationcytes

Project description:Expression analyses comparing c-Fos expressing keratinocytes vs non-expressing controls. Skin squamous cell carcinomas (SCCs) are the second most prevalent skin cancers. Chronic skin inflammation has been associated with the development of SCCs, but the contribution of skin inflammation to SCC development remains largely unknown. In this study we demonstrate that inducible expression of c-fos in the epidermis of adult mice is sufficient to promote inflammation-mediated epidermal hyperplasia leading to the development of pre-neoplastic lesions. Interestingly, c-Fos transcriptionally controls mmp10 and s100a7a15 expression in keratinocytes subsequently leading to CD4 T cell recruitment to the skin, thereby promoting epidermal hyperplasia. Combining inducible c-fos expression in the epidermis with a single dose of the carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) leads to the development of highly invasive SCCs, which are prevented by using the anti-inflammatory drug Sulindac. Moreover, human SCCs display a correlation between c-FOS expression and elevated levels of MMP10 and S100A15 proteins as well as CD4 T cell infiltration. Our studies demonstrate a bidirectional crosstalk between pre-malignant keratinocytes and infiltrating CD4 T cells in SCC development. Therefore, targeting inflammation along with the newly identified targets, such as MMP10 and S100A15, represent promising therapeutic strategies to treat SCCs. 5 different time points measured in triplicate comparing Dox-treated vs untreated c-FostetON keratinocytes

2013-09-05 | E-GEOD-50621 | biostudies-arrayexpress

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