Jonah Patel
Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that lacks a direct activating ligand and may be constitutively active or become active upon heterodimerization with other family members. Overexpression of HER2 is observed in approximately 15-30% of breast cancers and 10-30% of gastric/gastroesophageal cancers, contributing to tumour development and progression. This overexpression can result from numerous copies of the HER2 gene, leading to increased protein levels and receptor expression at the tumour cell surface. The discussion revolves around whether HER2 overexpression is merely a consequence of gene amplification or if it actively contributes to tumourigenesis. Understanding the mechanisms behind HER2 overexpression and its role in cancer is crucial for developing targeted therapies and improving patient outcomes.
| Characteristics | Values |
|---|---|
| Definition | Constitutive genes are continually transcribed, unlike facultative genes, which are only transcribed when needed. |
| Overexpression | Overexpression is when numerous copies of genes are created. |
| HER2 | Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-30% of breast cancers, 10-30% of gastric/gastroesophageal cancers, and some ovarian, endometrial, bladder, lung, colon, and head and neck cancers. |
| Treatment | HER2-directed therapies have been successful in treating patients with HER2-positive breast and gastric/gastroesophageal cancers. |
| Mechanism | Overexpression can be achieved by adding a constitutive promoter in front of the gene, keeping it always turned on. |
| Examples | Overexpression of MyoD causes fibroblasts to differentiate into muscle cells. Overexpression of eyeless results in the development of ectopic eyes. |
Explore related products
What You'll Learn
HER2 overexpression in cancers
Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family and possesses tyrosine kinase activity. HER2 overexpression is a well-known phenomenon in cancers, particularly in breast cancer, where it occurs in about 15-20% of cases, and gastric/gastroesophageal cancers, where it is seen in 10-30% of cases. HER2-positive breast cancers tend to grow and spread faster than HER2-negative cancers, but they are more likely to respond to treatments targeting the HER2 protein.
HER2 overexpression has also been observed in other cancers, such as ovarian, endometrial, bladder, lung, colon, and head and neck cancers. The introduction of HER2-directed therapies has significantly improved outcomes for patients with HER2-positive breast and gastric cancers. However, these therapies have not shown the same level of success in other cancers with HER2 overexpression.
The HER2 receptors exist as monomers on the cell surface. When ligands bind to their extracellular domains, HER2 proteins undergo dimerization and transphosphorylation of their intracellular domains. Interestingly, HER2 does not have a known direct activating ligand, and it may exist in a constitutively active state or become active upon heterodimerization with other family members such as HER1 and HER3. The dimerization of HER2 receptors results in the autophosphorylation of tyrosine residues within their cytoplasmic domains, initiating signaling pathways that lead to cell proliferation and tumorigenesis.
The detection of HER2 overexpression in cancers is crucial for guiding treatment decisions. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests are commonly used to determine HER2 status in breast cancers. Based on the results of these tests, cancers are classified as HER2-negative, HER2-ultralow, HER2-low, or HER2-positive. This classification helps determine the most effective treatment approach, with HER2-positive cancers being more responsive to drugs that target the HER2 protein.
In summary, HER2 overexpression plays a significant role in the development and progression of various cancers, particularly breast and gastric cancers. The introduction of targeted therapies has improved patient outcomes in these cancers. However, further research is needed to enhance the effectiveness of treatments for other cancers with HER2 overexpression.
Writing a School Constitution: A Step-by-Step Guide
You may want to see also
Constitutive gene expression
Gene expression is the process by which information from a gene is used to produce functional gene products, such as proteins or non-coding RNA molecules like tRNA and snRNA. This process is highly regulated, with various mechanisms controlling the timing, location, and amount of gene products in a cell. The regulation of gene expression is essential for cellular differentiation, development, and adaptability to environmental changes.
Constitutive genes are a type of gene that is always active and expressed in most cells. They are not subject to the same level of regulation as other genes and are transcribed continually. Ribosomal genes are a classic example of constitutive genes, as they are constantly transcribed because ribosomes require a continuous supply of proteins for synthesis. Other genes, like actin, GAPDH, and ubiquitin, are also considered constitutive as they are transcribed at a relatively constant rate.
In contrast, inducible genes are only expressed in response to specific stimuli or environmental changes. For instance, β-galactosidase proteins produced by E. coli are inducible genes that are expressed in higher quantities when "lactose" is present as an inducer. Facultative genes are another type of gene that is only transcribed when needed.
Overexpression of genes is a common technique used in research to produce larger quantities of target proteins. This can be achieved by inserting a constitutive promoter before the gene of interest, ensuring it remains active. Overexpression can also be used therapeutically, such as in the case of HER2 (Human Epidermal Growth Factor Receptor 2) overexpression in cancers. HER2-directed therapies have been developed to target HER2 overexpression in breast, gastric, and gastroesophageal cancers, improving patient outcomes.
The Power to Tax: Constitutional Conundrum
You may want to see also
Overexpression of STE12
Overexpression is a common technique used by researchers to produce a higher quantity of a target protein. This is done by creating multiple copies of a gene. One method to overexpress a gene is to place a constitutive promoter in front of it, which keeps the gene turned on at all times.
The STE12 gene encodes a helix-turn-helix transcription factor of the homeodomain family. STE12 is a sequence-specific DNA-binding transcription factor that activates transcription of genes involved in mating in response to pheromones. It is also involved in filamentous growth in response to nutrient limitation. STE12 is a key player in the morphogenetic programs initiated by environmental constraints, including pseudohyphal and invasive growth, dimorphic transitions, mating, and other specialized cell differentiations.
In the context of fungal MAPK signaling, STE12 is a target of the Fus3/Kss1 MAPK cascade, which regulates mating and invasive growth. STE12 binds to either pheromone response elements (PREs) in mating gene promoters or filamentation response elements (FREs) on filamentous growth-specific target genes. The binding of STE12 to these elements activates the expression of genes involved in mating or filamentous growth.
In summary, overexpression of STE12 leads to the constitutive activation of pheromone-responsive genes and is a powerful tool for studying the role of STE12 in various biological processes, including mating, filamentous growth, and fungal development and pathogenicity.
Constitution's Dual Legacy: Pro- and Anti-Slavery
You may want to see also
Explore related products
Overexpression to produce more target protein
Overexpression is a common method used to produce more target protein. It involves creating numerous copies of genes, which can be achieved by exploiting yeast transformation techniques or using vectors derived from the endogenous 2μ plasmid. This results in a pool of transformants, each containing a high-copy-number plasmid with an average of only five or six genes.
One way to overexpress a gene is by using a constitutive promoter, which keeps the gene “always turned on". This can be done by taking out the gene and putting it back in with a new promoter region that is either constitutive or inducible. Constitutive promoters are always active, while inducible promoters are responsive to environmental changes or the cell cycle stage.
Overexpression can also be achieved by activating a step in a pathway. For example, overexpressing MyoD causes fibroblasts to differentiate into muscle cells, and overexpressing eyeless leads to the development of ectopic eyes.
Overexpression has been used to identify drug targets and develop treatments, particularly in cancer. For instance, Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in approximately 15-30% of breast cancers and 10-30% of gastric/gastroesophageal cancers. Therapies targeting HER2 have dramatically improved patient outcomes in these cancers.
It is important to note that overexpression can sometimes lead to toxicity and gene silencing by the plant. Additionally, the availability of ribosomes may impact protein creation during overexpression.
Finding Constitutively Expressed Genes: A Guide
You may want to see also
Overexpression of MyoD
Overexpression of genes is a common technique in biological experiments. It involves creating multiple copies of a gene, usually by inserting a constitutive promoter in front of it, which keeps the gene turned on. Overexpression of MyoD, a master transcription factor in muscle development and differentiation, has been studied in the context of muscle cell identity and muscle differentiation.
MyoD is a 3D genome structure organizer for muscle cell identity. It functions as a "genome organizer," specifying a 3D genome architecture unique to muscle cell development. By comparing MyoD knockout and wild-type mice, researchers have provided support for the role of MyoD in 3D genome architecture in muscle stem cells.
Further studies have investigated the role of MyoD in muscle differentiation by analyzing the expression of downstream genes and long non-coding RNAs (lncRNAs). Overexpression of MyoD elevated the expression of the MyoG and MyHC genes, which are involved in muscle differentiation. Additionally, MyoD-mediated lncRNA expression analysis identified a novel lncRNA, lnc-AK143003, which negatively regulates muscle differentiation.
In summary, overexpression of MyoD has been studied in the context of muscle cell identity and muscle differentiation. It causes fibroblasts to differentiate into muscle cells and influences the expression of genes and lncRNAs involved in muscle development. Overexpressed MyoD binds to the same sites as endogenous MyoD, enhancing binding at physiologically relevant sites. These findings contribute to our understanding of the functional roles of transcription factors in muscle development and differentiation.
Understanding the Constitution: Why and How to Read It
You may want to see also
Frequently asked questions
Overexpression is when numerous copies of genes are created. It is often used as a screening tool to identify drug targets.
A constitutive gene is transcribed continually, whereas a facultative gene is only transcribed when needed.
An example of a constitutively active gene is p95, an aberrant form of HER2 found in some breast cancers.
Overexpression of drug targets can convey resistance to their corresponding drugs. For example, overexpression of HER2 is seen in about 20% of breast cancers and is associated with worse biological behaviour and clinical aggressiveness. Treatments targeting HER2 include lapatinib and trastuzumab, which have been shown to improve outcomes for patients with HER2-positive breast cancer.
