| Title |
Growth hormone-releasing hormone antagonists abolish the transactivation of human epidermal growth factor receptors in advanced prostate cancer models
|
|---|---|
| Published in |
Investigational New Drugs, July 2014
|
| DOI | 10.1007/s10637-014-0131-4 |
| Pubmed ID | |
| Authors |
Laura Muñoz-Moreno, M. Isabel Arenas, M. José Carmena, Andrew V. Schally, Juan C. Prieto, Ana M. Bajo |
| Abstract |
Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in a variety of cellular phenotypes related with tumorigenesis process. Human epidermal growth factor receptor family members (HER) such as EGFR and HER2 are involved in mitogenic signaling pathways implicated in the progression of prostate cancer. We analyzed the cross-talk between GHRH and EGF receptors in prostate cancer. The effects of GHRH in HER signaling were evaluated on human androgen-independent PC3 prostate cancer cells in vitro and GHRH antagonist in vitro and in nude mice xenografts of PC3 prostate cancer. Time-course studies indicated that GHRH had a stimulatory activity on both the expression of EGFR and HER2. GHRH analogues, JMR-132 and JV-1-38, endowed with antagonistic activity for GHRH receptors, abrogated the response to GHRH in PC3 cells. GHRH stimulated a rapid ligand-independent activation of EGFR and HER2 involving at least cAMP/PKA and Src family signaling pathways. GHRH also stimulated a slow ligand-dependent activation of EGFR and HER2 involving an extracellular pathway with an important role for ADAM. Preliminary results also revealed an increase of mRNA for GHRH and GHRH receptor induced by EGF. The inhibition of tumor growth, in vivo, was associated with a substantial reduction in the expression of mRNA and protein levels of EGFR and HER2 in the tumors. GHRH antagonist JV-1-38, significantly decreased the phosphorylated Src levels. The cross-talk between HER and GHRH-R may be impeded by combining drugs acting upon GHRH receptors and HER family members in human advanced prostate cancer. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 15 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 20% |
| Student > Bachelor | 2 | 13% |
| Student > Postgraduate | 2 | 13% |
| Researcher | 2 | 13% |
| Student > Ph. D. Student | 1 | 7% |
| Other | 2 | 13% |
| Unknown | 3 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 20% |
| Agricultural and Biological Sciences | 2 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 7% |
| Computer Science | 1 | 7% |
| Medicine and Dentistry | 1 | 7% |
| Other | 1 | 7% |
| Unknown | 6 | 40% |
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 17 July 2014.
All research outputs
#17,723,634
of 22,758,963 outputs
Outputs from Investigational New Drugs
#829
of 1,168 outputs
Outputs of similar age
#153,153
of 225,827 outputs
Outputs of similar age from Investigational New Drugs
#12
of 15 outputs
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