| Title |
BRAF Silencing by Short Hairpin RNA or Chemical Blockade by PLX4032 Leads to Different Responses in Melanoma and Thyroid Carcinoma Cells
|
|---|---|
| Published in |
Molecular Cancer Research, May 2008
|
| DOI | 10.1158/1541-7786.mcr-07-2001 |
| Pubmed ID | |
| Authors |
Elisa Sala, Luca Mologni, Silvia Truffa, Carlo Gaetano, Gideon E. Bollag, Carlo Gambacorti-Passerini |
| Abstract |
BRAF-activating mutations have been reported in several types of cancer, including melanoma ( approximately 70% of cases), thyroid (30-70%), ovarian (15-30%), and colorectal cancer (5-20%). Mutant BRAF has constitutive kinase activity and causes hyperactivation of the mitogen-activated protein kinase pathway. BRAF silencing induces regression of melanoma xenografts, indicating the essential role of BRAF for cell survival. We set up an inducible short hairpin RNA system to compare the role of oncogenic BRAF in thyroid carcinoma versus melanoma cells. Although BRAF knockdown led to apoptosis in the melanoma cell line A375, the anaplastic thyroid carcinoma cell ARO underwent growth arrest upon silencing, with little or no cell death. Reexpression of the thyroid differentiation marker, sodium iodide symporter, was induced after long-term silencing. The different outcome of BRAF down-regulation in the two cell lines was associated with an opposite regulation of p21(CIP1/WAF1) expression levels in response to the block of the BRAF mitogenic signal. These results were confirmed using a specific BRAF small-molecule inhibitor, PLX4032. Restoration of p21(CIP1/WAF1) expression rescued melanoma cells from death. Altogether, our data indicate that oncogenic BRAF inhibition can have a different effect on cell fate depending on the cellular type. Furthermore, we suggest that a BRAF-independent mechanism of cell survival exists in anaplastic thyroid cancer cells. |
Mendeley readers
The data shown below were compiled from readership statistics for 137 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 1% |
| United States | 2 | 1% |
| Unknown | 133 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 35 | 26% |
| Student > Ph. D. Student | 28 | 20% |
| Student > Master | 13 | 9% |
| Student > Bachelor | 12 | 9% |
| Other | 12 | 9% |
| Other | 21 | 15% |
| Unknown | 16 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 53 | 39% |
| Medicine and Dentistry | 27 | 20% |
| Biochemistry, Genetics and Molecular Biology | 27 | 20% |
| Chemistry | 9 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 1% |
| Other | 2 | 1% |
| Unknown | 17 | 12% |
Attention Score in Context
This research output has an Altmetric Attention Score of 16. 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 28 March 2023.
All research outputs
#2,070,901
of 23,485,204 outputs
Outputs from Molecular Cancer Research
#93
of 1,910 outputs
Outputs of similar age
#5,427
of 84,420 outputs
Outputs of similar age from Molecular Cancer Research
#1
of 15 outputs
Altmetric has tracked 23,485,204 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,910 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one has done particularly well, scoring higher than 95% 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 84,420 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.