Immunohistochemical Detection of Her2/neu Protein p185Her2
Immunohistochemical Detection of Her2/neu Protein p185Her2 in Feline Mammary Carcinoma
<b>Background</b>
A lot of work has been done recently to establish a Human Genome Model, a genetic map, physical map and comparative DNA sequence of human chromosomes. This work with the Human Genome Model cannot be achieved without a small part upon the parallel implementation of gene mapping projects in other species. One of these other species which has been associated with the human recently has been the feline (1). With exception to the primates, of the nonprimate mammalian species with developing comparative gene maps, the feline gene map (Felis Cat) displays the highest level of syntenic conservation with that of the humans gene map. The comparison of the human and feline map has shown many similarities between the human and feline, one of the most important similarities being the analogous relationship between felines and human diseases (2).
<b>Her2/neu Gene</b>
The human epidermal growth factor receptor 2 (Her2)/neu proto-oncogene, sometimes seen referred to as c-erbB2, encodes a 185kDa transmembrane tyrosine kinase receptor protein with homology to the epidermal growth factor (egfr) receptor (3).
The Her2/neu gene has an important role in normal cell growth and differentiation (6,7). The egfr family of receptors (including the Her2/neu gene) is involved in cell-to-cell and cell-to-stroma communication primarily through a process known as signal transduction, in which external growth factors, or ligands, affect the transcription of various genes by phosphorylating or dephosphorylating a series of transmembrane proteins and intracellular signaling intermediates, many of which possess enzymatic activity (4). Receptor activation requires three variables, a ligand, a receptor and a dimerization partner (5). After a ligand binds to a receptor, that receptor must interact with another receptor of identical or related structure in a process known as dimerization in order to trigger phosphorylation and activate signaling cascades (picture 2b). The activity of Her2/neu transmembrane receptor seems to be regulated by a 30kDa glycoprotein ligand (8). This phosphorylation and activation of signaling cascades will sometimes cause gene alterations, including gene amplification (9).
<b>p185Her2</b>
All normal cells contain two copies of the her2 gene and produce low levels of protein, also referred to as p185Her2 (10). It is mostly the gene amplification of the Her2/neu gene that has caused p185Her2 protein to overexpression in many cells. This overexpression is almost always the result of gene amplification (6, 11-14), an increase...