Human Epidermal Growth Factor Receptor Family (HER) in Gastric Cancer

The epidermal growth factor receptor family consists of four members with similar structures: HER1/erbB1, HER2/erbB2, HER3/erbB3 and HER4/erbB4. The genes encoded for Erb are proto-oncogenes, or precursor genes, which under normal conditions are present in all cells of an organism. Proto-oncogenes can be activated in several ways, most often it is through structural changes of the cell genome such as point mutation, translocation or amplification (Ghaderi, 2002). These receptors play an important role in the processes of proliferation and differentiation of normal cells. Hence, any aberrations in their structure or function can be the cause of tumor development and progression. All members of the epidermal growth factor receptor family have a similar structure with an extracellular domain linking the ligand, transmembrane domain and intracytoplasmic domain of the tyrosine kinase. The binding of the ligand to these receptors causes the creation of homodimers and heterodimers as well as the activation of downstream signaling pathways (Ghaderi, 2002). The ligand by inducing extracellular homo and heterodimerization of the ErbB receptors undergoes autophosphorylation using intracellular tyrosine residues by arranging the tyrosine kinase domains next to each other. The phosphorylated tyrosine endings of the cytoplasmic receptor act as sites that bind different intracytoplasmic transduction particles, which participate in the cellular response depending on ErbB stimulation (Tvorogov 2009). For this reason the HER family can contribute to tumor progression. Most research has shown a high level expression of the HER family members in patients suffering from gastric cancers (Ghaderi, 2002). Signaling through the HER pathway plays a fundamental role in the regulation of correct cell growth, proliferation, migration and takes part in such processes like the healing of wounds, cell repair and skin maintenance. However, it has been shown that signaling through the HER pathway plays a very important role in the growth process, replication, migration and survival of cancer cells. Since the HER signaling pathway cascades, causing the strengthening of the growth signal on progressing levels, small changes in the amount or activity of EGRF can significantly accelerate the development or progression of the tumor by facilitating cell replication and migration, and suppression of the apoptosis process (programmed cell death). What is more, many studies have shown that HER signaling, a fundamental factor in correct cell growth and repair, can be activated as a response to different therapies used to treat cancer, like chemotherapy or radiation therapy, and can