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Global expression profiling of sex cord stromal tumors from Men1 heterozygous mice identifies altered TGF‐β signaling, decreased Gata6 and increased Csf1r expression

Overview of attention for article published in International Journal of Cancer, December 2008
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Title
Global expression profiling of sex cord stromal tumors from Men1 heterozygous mice identifies altered TGF‐β signaling, decreased Gata6 and increased Csf1r expression
Published in
International Journal of Cancer, December 2008
DOI 10.1002/ijc.24057
Pubmed ID
Authors

Arne W. Mould, Russell Duncan, Magdalena Serewko‐Auret, Kelly A. Loffler, Christine Biondi, Michael Gartside, Graham F. Kay, Nicholas K. Hayward

Abstract

Heterozygous disruption of the Men1 gene predisposes mice to the development of multiple endocrine tumors, accurately mimicking the human MEN1 cancer predisposition syndrome. Additionally, Men1(+/-) mice frequently develop sex cord adenomas. The mechanism underlying the susceptibility of these mice to sex cord tumor development has not been fully determined, but data suggest it may involve transcriptional regulation of key growth promoting/repressing genes. To identify potential menin-regulated genes that may be important for tumor suppression in sex cord cells, we compared the global gene expression profiles of testis and ovary adenomas with other endocrine tumors of the pancreas and pituitary from Men1 heterozygous mice and with control tissues. Gonadal tumors clustered separately from pancreas and pituitary tumors with only a few genes (e.g., Cdkn2c) commonly dysregulated in all tumor types. Testis and ovary tumors displayed a higher level of transcriptional similarity to each other than they did to their respective control tissues. Among genes that had decreased expression in tumors was significant over-representation of genes associated with the TGF-beta, hedgehog and Wnt signaling, indicating that loss of menin function affects these pathways at the level of transcription. Aberrant protein expression in Leydig and granulosa cells of 2 transcriptionally dysregulated gene products, Gata6 and Csf1r were confirmed by immunohistochemistry. We propose that sex cord tumor susceptibility in Men1(+/-) mice involves deregulated cell proliferation due to dysregulation of multiple cell growth regulating genes including: reduced Cdkn2c transcription, loss of TGF-beta pathway tumor suppressor function (e.g., Gata6) and transcriptional activation of Csf1r.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 36%
Other 1 9%
Professor 1 9%
Student > Bachelor 1 9%
Student > Ph. D. Student 1 9%
Other 1 9%
Unknown 2 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 27%
Medicine and Dentistry 3 27%
Agricultural and Biological Sciences 2 18%
Nursing and Health Professions 1 9%
Unknown 2 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 December 2008.
All research outputs
#17,286,379
of 25,374,917 outputs
Outputs from International Journal of Cancer
#10,142
of 12,204 outputs
Outputs of similar age
#152,560
of 179,378 outputs
Outputs of similar age from International Journal of Cancer
#70
of 77 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,204 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 12th percentile – i.e., 12% of its peers scored the same or lower than it.
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We're also able to compare this research output to 77 others from the same source and published within six weeks on either side of this one. This one is in the 3rd percentile – i.e., 3% of its contemporaries scored the same or lower than it.