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Sunday, October 6, 2019

The Significance of HER 2 Receptor Expression in Breast Cancer Tissue Essay

The Significance of HER 2 Receptor Expression in Breast Cancer Tissue - Essay Example It has been found that up to 25% of breast cancer patients will have an amplification of the HER2/neu gene or an increase in HER2 production (Songdong et al, 2006). Additionally, any patient with amplification of this gene will generally have an increased likelihood of cancer recurrence and a more aggressive form of cancer (Meng et al, 2004). The purpose of this paper is to discuss further the significance of HER2 receptor expression in breast cancers, and describe the laboratory methods of detecting this protein in detail. This will give an overview of the complications of overexpression of HER2 and allow the reader an insight into how important the HER2 protein and the HER2/neu gene are in breast cancers and how the detection of these can allow for insight into breast cancer and can lead to a reduction in the number of fatalities from breast cancer. Significance of HER2 in Breast Cancers The significance of the HER2 protein in breast cancers has been widely discussed in the literat ure. As previously mentioned, 'Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis' (Songdong et al, 2006, p17361). ... ding two cysteine rich domains, a transmembrane domain, and an intracellular domain, consisting of a juxtamembrane region, a tyrosine kinase domain, and a carboxyl tail harboring autophosphorylation sites' (Brennan, 2002, p328). It is the binding of certain cognate cofactors to this trans-membrane receptor that regulates cell growth and differentiation, which occurs through the activation of receptor tyrosine kinases (Brennan, 2002). This is a type of signal transduction pathway, which in the case of HER2 involves ogliomerization (Meng et al, 2004) and dimerization (Brennan, 2002). On a study of rats by Bargmann et al (1986), it was found that the neu gene (which is classed as protooncogene) is converted to the aggressive oncogene associated with overproduction of HER2 by a single point mutation at position 664 of the protein sequence. This mutation is from a valine to the negatively-charged glutamate, and is associated with an increase of the liklihood that the receptor will form ag gregates. Unfortunately, the mutation at position 664 is not found in humans, but this has given clues as to the mechanism of the HER2 protein in causing the more aggressive forms of breast cancers. `Figure 1 shows the pathway that HER2 plays a role in within the confines of breast cancer. Figure 1 – Cross-talk between signal transduction pathways and ER signaling in endocrine resistant breast cancer, with opportunities for targeted intervention (Ellis & Ma, 2007, p107) An insight into these pathways allows for recognition of interventions that can be used to negate the effects of the increased production of HER2. From figure 1, it is evident that HER2 is surface-membrane protein with a critical role in the MAPK/ERK signal transduction pathway. The MAPK/ERK pathway passes a signal from

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