| Title |
PDE5 expression in human thyroid tumors and effects of PDE5 inhibitors on growth and migration of cancer cells
|
|---|---|
| Published in |
Endocrine, April 2015
|
| DOI | 10.1007/s12020-015-0586-x |
| Pubmed ID | |
| Authors |
Marialuisa Sponziello, Antonella Verrienti, Francesca Rosignolo, Roberta Francesca De Rose, Valeria Pecce, Valentina Maggisano, Cosimo Durante, Stefania Bulotta, Giuseppe Damante, Laura Giacomelli, Cira Rosaria Tiziana Di Gioia, Sebastiano Filetti, Diego Russo, Marilena Celano |
| Abstract |
Recent studies have revealed in normal thyroid tissue the presence of the transcript of several phosphodiesterases (PDEs), enzymes responsible for the hydrolysis of cyclic nucleotides. In this work, we analyzed the expression of PDE5 in a series of human papillary thyroid carcinomas (PTCs) presenting or not BRAF V600E mutation and classified according to ATA risk criteria. Furthermore, we tested the effects of two PDE5 inhibitors (sildenafil, tadalafil) against human thyroid cancer cells. PDE5 gene and protein expression were analyzed in two different cohorts of PTCs by real-time PCR using a TaqMan micro-fluid card system and Western blot. MTT and migration assay were used to evaluate the effects of PDE5 inhibitors on proliferation and migration of TPC-1, BCPAP, and 8505C cells. In a first series of 36 PTCs, we found higher expression levels of PDE5A in tumors versus non-tumor (normal) tissues. PTCs with BRAF mutation showed higher levels of mRNA compared with those without mutation. No significant differences were detected between subgroups with low and intermediate ATA risk. Upregulation of PDE5 was also detected in tumor tissue proteins. Similar results were obtained analyzing the second cohort of 50 PTCs. Moreover, all tumor tissues with high PDE5 levels showed reduction of Thyroglobulin, TSH receptor, Thyroperoxidase, and NIS transcripts. In thyroid cancer cells in vitro, sildenafil and tadalafil determined a reduction of proliferation and cellular migration. Our findings demonstrate for the first time an overexpression of PDE5 in PTCs, and the ability of PDE5 inhibitors to block the proliferation of thyroid cancer cells in culture, therefore, suggesting that specific inhibition of PDE5 may be proposed for the treatment of these tumors. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Italy | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 19% |
| Student > Master | 6 | 16% |
| Student > Bachelor | 5 | 14% |
| Student > Ph. D. Student | 4 | 11% |
| Professor > Associate Professor | 4 | 11% |
| Other | 6 | 16% |
| Unknown | 5 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 27% |
| Medicine and Dentistry | 8 | 22% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 14% |
| Agricultural and Biological Sciences | 4 | 11% |
| Psychology | 2 | 5% |
| Other | 2 | 5% |
| Unknown | 6 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 06 April 2015.
All research outputs
#13,737,330
of 22,797,621 outputs
Outputs from Endocrine
#792
of 1,681 outputs
Outputs of similar age
#132,263
of 264,242 outputs
Outputs of similar age from Endocrine
#8
of 26 outputs
Altmetric has tracked 22,797,621 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 26 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 69% of its contemporaries.