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Attention Score in Context
| Title |
Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis
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|---|---|
| Published in |
Breast Cancer Research, December 2014
|
| DOI | 10.1186/s13058-014-0501-z |
| Pubmed ID | |
| Authors |
Vikram B Wali, Maureen Gilmore-Hebert, Ramanaiah Mamillapalli, Jonathan W Haskins, Kari J Kurppa, Klaus Elenius, Carmen J Booth, David F Stern |
| Abstract |
IntroductionHuman Epidermal Growth Factor Receptor (ERBB4/HER4) belongs to the Epidermal Growth Factor receptor/ERBB family of receptor tyrosine kinases. While ERBB1, ERBB2 and ERBB3 are often overexpressed or activated in breast cancer, and are oncogenic, the role of ERBB4 in breast cancer is uncertain. Some studies suggest a tumor suppressor role of ERBB4, while other reports suggest an oncogenic potential. Alternative splicing of ERBB4 yields four major protein products, these spliced isoforms differ in the extracellular juxtamembrane domain (JM-a versus JM-b) and cytoplasmic domain (CYT-1 versus CYT-2). Two of these isoforms, JM-a CYT-1 and JM-a CYT-2, are expressed in the mammary gland. Failure to account for isoform-specific functions in previous studies may account for conflicting reports on the role of ERBB4 in breast cancer.MethodsWe have produced mouse mammary tumour virus (MMTV) -ERBB4 transgenic mice to evaluate potential developmental and carcinogenic changes associated with full length (FL) JM-a ERBB4 CYT-1 versus ERBB4 CYT-2. Mammary tissue was isolated from transgenic mice and sibling controls at various developmental stages for whole mount analysis, RNA extraction, and immunohistochemistry. To maintain maximal ERBB4 expression, transgenic mice were bred continuously for a year after which mammary glands were isolated and analyzed.ResultsOverexpressing FL CYT-1 isoform resulted in suppression of mammary ductal morphogenesis which was accompanied by decreased number of mammary terminal end buds (TEBs) and Ki-67 positive cells within TEBs, while FL CYT-2 isoform had no effect on ductal growth in pubescent mice. The suppressive ductal phenotype in CYT-1 mice disappeared after mid-pregnancy, and subsequent developmental stages showed no abnormality in mammary gland morphology or function in CYT-1 or CYT-2 transgenic mice. However, sustained expression of FL CYT-1 isoform resulted in formation of neoplastic mammary lesions, suggesting a potential oncogenic function for this isoform.ConclusionsTogether, we present isoform-specific roles of ERBB4 during puberty and early pregnancy, and reveal a novel oncogenic property of CYT-1 ERBB4. The results may be exploited to develop better therapeutic strategies in breast cancer. |
Mendeley readers
The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Denmark | 1 | 2% |
| Unknown | 44 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 26% |
| Professor | 4 | 9% |
| Student > Bachelor | 4 | 9% |
| Student > Master | 4 | 9% |
| Student > Doctoral Student | 3 | 7% |
| Other | 7 | 15% |
| Unknown | 12 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 12 | 26% |
| Biochemistry, Genetics and Molecular Biology | 11 | 24% |
| Medicine and Dentistry | 5 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 9% |
| Nursing and Health Professions | 2 | 4% |
| Other | 1 | 2% |
| Unknown | 11 | 24% |
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 18 December 2014.
All research outputs
#22,759,452
of 25,373,627 outputs
Outputs from Breast Cancer Research
#1,882
of 2,052 outputs
Outputs of similar age
#296,868
of 347,654 outputs
Outputs of similar age from Breast Cancer Research
#43
of 52 outputs
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So far Altmetric has tracked 2,052 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 52 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.