Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of BRCA1 wild type and mutant human breast tumors to examine expression of ER-alpha

ABSTRACT: Looking at the expression of ER alpha in BRCA1 and mutant tumours

ORGANISM(S): Homo sapiens

SUBMITTER: Alison Hosey

PROVIDER: E-TABM-366 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer.

Hosey Alison M AM Gorski Julia J JJ Murray Margaret M MM Quinn Jennifer E JE Chung Wen Y WY Stewart Gail E GE James Colin R CR Farragher Susan M SM Mulligan Jude M JM Scott Alistair N AN Dervan Peter A PA Johnston Patrick G PG Couch Fergus J FJ Daly Peter A PA Kay Elaine E McCann Amanda A Mullan Paul B PB Harkin D Paul DP

Journal of the National Cancer Institute 20071113 22

<h4>Background</h4>BRCA1-mutant breast tumors are typically estrogen receptor alpha (ER alpha) negative, whereas most sporadic tumors express wild-type BRCA1 and are ER alpha positive. We examined a possible mechanism for the observed ER alpha-negative phenotype of BRCA1-mutant tumors.<h4>Methods</h4>We used a breast cancer disease-specific microarray to identify transcripts that were differentially expressed between paraffin-embedded samples of 17 BRCA1-mutant and 14 sporadic breast tumors. We ...[more]

PMID: 18000219

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Project description:The DosR regulon in Mycobacterium tuberculosis is involved in respiration-limiting conditions and its induction is controlled by two histidine kinases, DosS and DosT. Recent experimental evidence indicates DosS senses either molecular oxygen or a redox change. This report demonstrates that DosS responds to a reduced electron transport system (ETS), although this does not rule out a role for oxygen in silencing signaling. Under aerobic conditions induction of the DosR regulon by DosS but not DosT was observed after the addition of ascorbate, a powerful cytochrome c reductant, demonstrating DosS responds to a redox signal even in the presence of high oxygen tension. During hypoxic conditions regulon induction was attenuated by treatment with compounds that occluded electron flow into the menaquinone pool or decreased the size of the menaquinone pool itself. Increased regulon expression during hypoxia was observed when exogenous menaquinone was added, demonstrating the menaquinone pool is a limiting factor in regulon induction. Taken together these data indicate that a reduced menaquinone pool directly or indirectly triggers induction of the DosR regulon via DosS. Biochemical analysis of menaquinones upon entry into hypoxic/anaerobic conditions demonstrated the disappearance of the unsaturated species and low-level maintenance of the mono-saturated menaquinone. Relative to the unsaturated form, an analog of the saturated form is better able to induce signaling via DosS, rescue inhibition of menaquinone synthesis, and is less toxic. The menaquinone pool is central to the ETS and therefore provides a mechanistic link between the respiratory state of the bacilli and DosS signaling. Aerobically growing logarithmic phase DosS and DosT mutant strains were analyzed after treatment with the cytochrome c reductant ascorbate to examine the effect on DosR signaling caused by reducing the electron transport system. Experiments were repeated in triplicate (dosT mutant) or duplicate (dosS mutant).

Dataset Information

Transcription profiling of BRCA1 wild type and mutant human breast tumors to examine expression of ER-alpha

Publications

Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer.

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