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Nitric Oxide Synthase and Breast Cancer: Role of TIMP-1 in NO-mediated Akt Activation

Overview of attention for article published in PLOS ONE, September 2012
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (69th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (63rd percentile)

Mentioned by

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2 tweeters
patent
1 patent

Citations

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40 Dimensions

Readers on

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41 Mendeley
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Title
Nitric Oxide Synthase and Breast Cancer: Role of TIMP-1 in NO-mediated Akt Activation
Published in
PLOS ONE, September 2012
DOI 10.1371/journal.pone.0044081
Pubmed ID
Authors

Lisa A. Ridnour, Kimberly M. Barasch, Alisha N. Windhausen, Tiffany H. Dorsey, Michael M. Lizardo, Harris G. Yfantis, Dong H. Lee, Christopher H. Switzer, Robert Y. S. Cheng, Julie L. Heinecke, Ernst Brueggemann, Harry B. Hines, Chand Khanna, Sharon A. Glynn, Stefan Ambs, David A. Wink

Abstract

Prediction of therapeutic response and cancer patient survival can be improved by the identification of molecular markers including tumor Akt status. A direct correlation between NOS2 expression and elevated Akt phosphorylation status has been observed in breast tumors. Tissue inhibitor matrix metalloproteinase-1 (TIMP-1) has been proposed to exert oncogenic properties through CD63 cell surface receptor pathway initiation of pro-survival PI3k/Akt signaling. We employed immunohistochemistry to examine the influence of TIMP-1 on the functional relationship between NOS2 and phosphorylated Akt in breast tumors and found that NOS2-associated Akt phosphorylation was significantly increased in tumors expressing high TIMP-1, indicating that TIMP-1 may further enhance NO-induced Akt pathway activation. Moreover, TIMP-1 silencing by antisense technology blocked NO-induced PI3k/Akt/BAD phosphorylation in cultured MDA-MB-231 human breast cancer cells. TIMP-1 protein nitration and TIMP-1/CD63 co-immunoprecipitation was observed at NO concentrations that induced PI3k/Akt/BAD pro-survival signaling. In the survival analysis, elevated tumor TIMP-1 predicted poor patient survival. This association appears to be mainly restricted to tumors with high NOS2 protein. In contrast, TIMP-1 did not predict poor survival in patient tumors with low NOS2 expression. In summary, our findings suggest that tumors with high TIMP-1 and NOS2 behave more aggressively by mechanisms that favor Akt pathway activation.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 1 2%
India 1 2%
Switzerland 1 2%
Unknown 38 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 24%
Student > Ph. D. Student 8 20%
Student > Master 7 17%
Student > Bachelor 5 12%
Student > Doctoral Student 3 7%
Other 6 15%
Unknown 2 5%
Readers by discipline Count As %
Agricultural and Biological Sciences 13 32%
Medicine and Dentistry 9 22%
Biochemistry, Genetics and Molecular Biology 9 22%
Veterinary Science and Veterinary Medicine 1 2%
Nursing and Health Professions 1 2%
Other 4 10%
Unknown 4 10%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 23 October 2018.
All research outputs
#5,230,345
of 17,351,915 outputs
Outputs from PLOS ONE
#58,932
of 164,775 outputs
Outputs of similar age
#39,752
of 138,750 outputs
Outputs of similar age from PLOS ONE
#1,284
of 3,728 outputs
Altmetric has tracked 17,351,915 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 164,775 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.5. This one has gotten more attention than average, scoring higher than 63% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 138,750 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 3,728 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.