Overexpression describes when a gene produces an unusually high amount of its corresponding protein or RNA molecule. This represents an imbalance in a cell’s normal, regulated processes. An excess of a gene’s product can have consequences, influencing cellular behavior and biological systems.
Understanding Overexpression
Gene expression is the intricate process by which information from a gene, encoded in DNA, is used to synthesize a functional gene product, such as a protein or RNA molecule. This process typically involves two main steps: transcription, where DNA is copied into messenger RNA (mRNA), and translation, where mRNA is used as a template to build proteins. Cells maintain precise control over these steps to ensure appropriate levels of each gene product.
Overexpression occurs when a gene produces protein or RNA significantly exceeding normal levels in healthy cells. This surplus can disrupt cellular functions, leading to stress or altered states. The excess product might interfere with pathways, bind to too many targets, or overwhelm the cell’s capacity.
Why Overexpression Occurs
Overexpression can arise through gene amplification, where a cell acquires multiple copies of a gene. Instead of the usual two copies, a cell might have dozens or hundreds. Each additional gene copy acts as another template, leading to greater output of the corresponding protein or RNA. This increases gene product levels.
Mutations within a gene’s regulatory regions can also trigger overexpression. These regions, like promoters and enhancers, act as “on switches” dictating when and how strongly a gene is expressed. A change in their DNA sequence can make the switch hyperactive, causing the gene to be continuously turned on. For example, a promoter mutation might allow it to bind transcription factors more efficiently, leading to constant gene activation.
Another mechanism involves issues with cellular machinery that degrades proteins. Cells have systems, like the ubiquitin-proteasome pathway, that tag old or misfolded proteins for destruction, maintaining appropriate levels. Defects in these pathways mean overproduced proteins may not break down efficiently, causing them to accumulate. This accumulation results in an overabundance of the protein.
Overexpression in Disease
Overexpression plays a role in the development and progression of various diseases, particularly cancer. Many cancers feature overexpressed oncogenes, which promote uncontrolled cell growth and division. The HER2 gene, for example, is overexpressed in approximately 15-20% of breast cancers. This excess HER2 protein on cancer cells sends constant growth signals, driving tumor proliferation and survival.
The epidermal growth factor receptor (EGFR) is often overexpressed in several cancer types, including lung, colorectal, and head and neck cancers. High EGFR levels lead to increased cell growth, survival, and metastasis. The MYC gene, a transcription factor regulating cell cycle progression, is also frequently overexpressed in various cancers, such as Burkitt lymphoma and neuroblastoma, contributing to rapid cell division and tumor formation.
Beyond cancer, overexpression is implicated in neurological conditions. For example, overexpressed alpha-synuclein protein is linked to Parkinson’s disease. An excess can form abnormal clumps called Lewy bodies, disrupting brain cell function. Similarly, overexpressed and abnormally modified tau protein forms neurofibrillary tangles in conditions like Alzheimer’s disease, impairing neuronal transport and communication.
Overexpression in Research and Medicine
Understanding overexpression has advanced scientific research and medical applications. In biotechnology, cells are engineered to overexpress specific proteins for large-scale production. This method produces therapeutic proteins like human insulin, growth hormones, and monoclonal antibodies for autoimmune diseases and cancers. Cells like bacteria, yeast, or mammalian cell lines are modified to become efficient biological factories, producing high quantities of these proteins.
The study of overexpression also helps identify drug targets and develop targeted therapies. By pinpointing overexpressed proteins in diseases like cancer, scientists can design drugs to reduce their activity or levels. For instance, in HER2-positive breast cancer, drugs like trastuzumab (Herceptin) are antibodies that bind to overexpressed HER2 receptors, blocking signaling and marking cancer cells for immune destruction. Tyrosine kinase inhibitors, such as gefitinib or erlotinib, block overactive signaling pathways of overexpressed EGFR in various cancers, inhibiting tumor growth.