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The cells identified by the special immunohistochemical stain are shown to overexpress a 185 kD glycoprotein that spans the cell membrane and has tyrosine kinase activity in the intracellular domain. Which of the following is the most likely function of this protein?
The HER2 oncogene codes for a human epidermal growth factor receptor with tyrosine kinase activity in the intracellular domain. It is known to play a role in the activation of transduction pathways that control epithelial growth and differentiation. Epithelial cell carcinomas that overexpress HER2 demonstrate increased proliferation and resistance to apoptosis. Consequently, HER2-positive breast cancers have a higher risk of disease recurrence and worse prognosis compared to HER2-negative breast cancers. Trastuzumab (a monoclonal antibody against HER2) is used to treat women who test positive for overexpression of the HER2 oncogene.
(Choice B) Estrogen and progesterone receptors are intracellular receptors that are frequently overexpressed in patients with breast cancer. Stimulation of these hormone receptors increases cellular proliferation, and patients with hormone-receptor-positive breast cancer are treated with antiestrogen medications to suppress tumor growth.
(Choice C) Intercellular binding is mediated by cell surface proteins such as intercellular adhesion molecules (ICAMs), selectins, and numerous others. Many adhesion proteins, including ICAMS, also play a role in signal transduction.
(Choice D) Various hormones, cytokines, and other stimuli can induce cytokine release from a number of cell types. One example of a receptor that induces cytokine release is the Toll-like receptor, which detects conserved microbial molecular structures.
(Choice E) Clathrin is an intracellular protein that helps form rounded vesicles in the cytoplasm. Clathrin-coated vesicles help mediate intracellular trafficking and endocytosis.
Educational objective:
The HER2 oncogene encodes for a transmembrane glycoprotein with intrinsic tyrosine kinase activity and is a member of the family of epidermal growth factor receptors. Overexpression of this protein is associated with a worse prognosis and increased risk of disease recurrence.