Mutationally Activated BRAFV600E Elicits Papillary Thyroid Cancer in the Adult Mouse
1.1: Scientific Background
In this article, the authors have described that the thyroid cancer is a frequent tumour which emerge from the endocrine system and, recently, in 2010 it has been diagnosed in almost 45000 cases in USA. This kind of cancer usually does not rapidly increase in body. However, in the recent documentation the number of cases increased, especially in women, which is an alarming situation.
Within this context, Papillary Thyroid Carcinoma (PTC) has been identified in many of histological sub-types, almost 80% among all cases of main tumour. The most common treatment for this type of cancer is surgery and after radiotherapy, as both methods of treatment is normally helpful. However, in this research authors seems interested about the genetics, which affects in thyroid cancer and how it can influence the pathophysiology as well as how the therapy for this illness has been evolved.
Furthermore, they have explained that somatic genetic modifications have been noticed in PTC (Papillary Thyroid Carcinoma), and it has been related to almost 45% cases linked to BRAF, which is correlated with malign tumour. Also, PTC has been detected in different kinds of cancer, such as melanoma and colon cancer. The mutation that is usually found is T1799 to A is a transversion, which has been in exon 15 and has encoded BRAF. The activation of mutation is occurred because the BRAFV600E provokes MEK-ERK kinase activity and modifies the gene expression, which is a significant cause of cancer in the cell and the abnormal behaviour in the body. Additionally, the pharmacological therapy has been inhibited, because it has been blocked by PLX-4032, and the tumour has been decreased for patients with thyroid cancer. Although, it has also been suggested in data, that BRAFV600E is required to preserve PTC.
1.2: Transgenic Mice
The authors have explained about the importance of BRAF(CA) mice, which are crucial to express Cre-mediated allele of BRAF. This was also reported as a model in lung cancer and melanoma. After the usage of this method on mice with specific expression to thyroid cancer, which is called thyrocyte-specific expression, and it has demonstrated a conditional Cre recombination, this enzyme is stated as CreER T2 and it has been under the regulation of thyroglobulin promoter which is thyro::CreER T2. The diagram in this connection, can contribute in the better understanding of this explanation, because it is widely accepted that Cre/loxP system can be used to remove DNA sequences, and it will block the gene transcription. The scientist desires to activate the target gene because it is more relevant to the study.
Furthermore, authors of this paper have investigated about the effects generated by BRAFV600E expression in adult thyroid. In this connection, authors have described that, after BRAFV600E expression, the size and conformation of thyroid follicles has been dramatically modified and it was demonstrated by mice, because the mice were affected of ...