16.7 Cancer and Gene Regulation
3 min read•june 14, 2024
Cancer develops when gene regulation goes awry. Mutations in growth-promoting genes or can lead to uncontrolled cell division. Environmental factors and epigenetic changes also play a role in altering gene expression and initiating cancer.
The cell cycle is tightly controlled by proteins like and . Disruptions in these regulators can cause excessive cell division. Understanding these molecular pathways has led to targeted cancer therapies and personalized medicine approaches.
Cancer and Gene Regulation
Gene expression in cancer development
Top images from around the web for Gene expression in cancer development
Frontiers | Integrative Genomic and Transcriptomic Analyses of Tumor Suppressor Genes and Their ... View original
Is this image relevant?
Overview of Cancer | Boundless Anatomy and Physiology View original
Is this image relevant?
Cancer: Is DNA methylation of tumour suppressor genes epigenetic? | eLife View original
Is this image relevant?
Frontiers | Integrative Genomic and Transcriptomic Analyses of Tumor Suppressor Genes and Their ... View original
Is this image relevant?
Overview of Cancer | Boundless Anatomy and Physiology View original
Is this image relevant?
1 of 3
Top images from around the web for Gene expression in cancer development
Frontiers | Integrative Genomic and Transcriptomic Analyses of Tumor Suppressor Genes and Their ... View original
Is this image relevant?
Overview of Cancer | Boundless Anatomy and Physiology View original
Is this image relevant?
Cancer: Is DNA methylation of tumour suppressor genes epigenetic? | eLife View original
Is this image relevant?
Frontiers | Integrative Genomic and Transcriptomic Analyses of Tumor Suppressor Genes and Their ... View original
Is this image relevant?
Overview of Cancer | Boundless Anatomy and Physiology View original
Is this image relevant?
1 of 3
- Cancer arises from the accumulation of mutations in genes that regulate cell growth and division
- promote cell growth and division (, )
- Mutations in proto- can convert them into oncogenes leading to uncontrolled cell growth
- Tumor suppressor genes inhibit cell growth and division (, )
- Mutations in tumor suppressor genes can inactivate them allowing uncontrolled cell growth
- promote cell growth and division (, )
- Epigenetic changes can also contribute to altered gene expression in cancer cells
- addition of methyl groups to DNA can silence tumor suppressor genes
- changes in histone proteins can affect gene expression promoting or suppressing cancer development (, )
- Environmental factors can influence cancer development
- Exposure to can cause DNA damage and mutations leading to cancer initiation
Gene regulation and cell cycle
- The cell cycle is tightly regulated by various proteins including and
- Cyclins regulate the progression of the cell cycle (, )
- are enzymes that when bound to cyclins phosphorylate target proteins to control cell cycle progression (, )
- Disruptions in the expression of cell cycle regulators can lead to uncontrolled cell division
- Overexpression of cyclins or can cause cells to divide too frequently
- Inactivation of inhibitors such as and can also lead to uncontrolled cell division
- The p53 tumor suppressor gene plays a crucial role in regulating the cell cycle and preventing cancer development
- p53 induces cell cycle arrest or in response to DNA damage or cellular stress
- Mutations in p53 can lead to the accumulation of DNA damage and the development of cancer ()
- monitor the cell cycle and can halt progression if abnormalities are detected
Cancer progression and metastasis
- is the formation of new blood vessels that supply tumors with nutrients and oxygen, promoting growth
- occurs when cancer cells spread from the primary tumor to other parts of the body
- The , including surrounding non-cancerous cells and extracellular matrix, influences cancer progression
- activation in cancer cells allows for unlimited replication potential by maintaining telomere length
Gene insights for cancer drugs
- Understanding the molecular pathways involved in cancer development has led to the development of targeted therapies
- target overactive kinases such as in chronic myeloid leukemia ()
- target specific proteins on the surface of cancer cells such as in breast cancer ()
- Epigenetic therapies aim to reverse aberrant epigenetic changes in cancer cells
- prevent the silencing of tumor suppressor genes by blocking DNA methylation ()
- promote the expression of tumor suppressor genes by increasing histone acetylation ()
- Personalized medicine approaches use genetic and molecular profiling to tailor cancer treatments to individual patients
- Identification of specific mutations or gene expression patterns can guide the selection of targeted therapies ( mutations in lung cancer)
- Monitoring of cancer biomarkers can help assess treatment response and detect relapse ( in prostate cancer)
Key Terms to Review (43)
Acetylation: Acetylation is a biochemical process that involves the addition of an acetyl group (COCH₃) to a molecule, often altering its function and activity. This modification plays a critical role in regulating various cellular processes, including gene expression and protein function, making it an essential aspect of both enzymatic activity and cellular regulation.
Acetylcholinesterase: Acetylcholinesterase is an enzyme that breaks down the neurotransmitter acetylcholine in the synaptic cleft. It plays a crucial role in terminating synaptic transmission and allowing muscle relaxation.
Aliphatic hydrocarbons: Aliphatic hydrocarbons are organic compounds consisting solely of carbon and hydrogen atoms arranged in straight or branched chains, but not containing aromatic rings. They can be saturated (alkanes) or unsaturated (alkenes and alkynes).
Angiogenesis: Angiogenesis is the biological process through which new blood vessels form from existing ones. This process is crucial for growth and development, but it becomes particularly significant in the context of cancer, as tumors require a blood supply to grow and spread. When angiogenesis is activated by certain signals, it can contribute to the progression of cancer by enhancing nutrient and oxygen delivery to tumor cells.
Apoptosis: Apoptosis is a programmed cell death process that occurs in multicellular organisms, characterized by a series of tightly regulated events leading to the elimination of unwanted or damaged cells. This mechanism is crucial for maintaining tissue homeostasis, regulating the cell cycle, and ensuring proper development and functioning of organisms.
Azacitidine: Azacitidine is a nucleoside analog that is primarily used as a chemotherapy drug in the treatment of certain types of cancer, particularly myelodysplastic syndromes and acute myeloid leukemia. It works by inhibiting DNA methylation, which plays a crucial role in gene regulation, thereby reversing abnormal gene silencing often associated with cancer progression.
BCR-ABL: BCR-ABL is a fusion gene created by the translocation of chromosome 9 and chromosome 22, which results in the combination of the BCR gene from chromosome 22 and the ABL gene from chromosome 9. This abnormal gene encodes for a tyrosine kinase protein that is constitutively active, leading to uncontrolled cell division and is primarily associated with chronic myeloid leukemia (CML). Understanding BCR-ABL is crucial as it links genetic mutations to cancer development and highlights the impact of gene regulation on cellular processes.
Carcinogens: Carcinogens are substances or agents that can cause cancer in living tissue. They may work by directly damaging the DNA in cells, leading to mutations that can promote uncontrolled cell growth. Understanding carcinogens is essential for comprehending the complex relationship between environmental factors and gene regulation, as they can influence the expression of oncogenes and tumor suppressor genes.
CDK4: CDK4, or Cyclin-Dependent Kinase 4, is an important enzyme that plays a crucial role in regulating the cell cycle, specifically the transition from the G1 phase to the S phase. This kinase partners with cyclins to phosphorylate target proteins, facilitating cell cycle progression. In the context of cancer, CDK4 can become dysregulated, leading to uncontrolled cell division and tumor growth.
CDK6: CDK6, or Cyclin-Dependent Kinase 6, is a crucial protein that plays a key role in regulating the cell cycle, particularly the transition from the G1 phase to the S phase. This kinase interacts with cyclins to drive cell proliferation and is essential for the proper progression of cells through the cell cycle. Additionally, alterations in CDK6 activity can lead to uncontrolled cell division and are implicated in various cancers, highlighting its importance in gene regulation and cancer biology.
CDKs: Cyclin-dependent kinases (CDKs) are a family of protein kinases that play a crucial role in regulating the cell cycle by phosphorylating specific target proteins. They are activated when bound to cyclins, which are proteins that fluctuate in concentration throughout the cell cycle. CDKs ensure the proper timing and progression of the cell cycle, making them essential for normal cell division and functioning.
Checkpoint proteins: Checkpoint proteins are critical regulators in the cell cycle that ensure proper progression through different phases by monitoring and repairing DNA damage, as well as assessing whether conditions are favorable for cell division. These proteins play a vital role in maintaining genomic integrity and preventing uncontrolled cell proliferation, which is a hallmark of cancer. By detecting problems at specific checkpoints, these proteins can halt the cell cycle to allow for repair or trigger apoptosis if the damage is irreparable.
Cyclin D: Cyclin D is a regulatory protein that plays a crucial role in controlling the cell cycle, specifically in the transition from the G1 phase to the S phase. It acts by activating cyclin-dependent kinases (CDKs), which are essential for driving the cell through key checkpoints in the cell cycle, responding to growth signals and regulating cellular proliferation.
Cyclin E: Cyclin E is a regulatory protein that plays a crucial role in cell cycle progression, particularly in the transition from the G1 phase to the S phase. It binds to and activates cyclin-dependent kinase 2 (CDK2), driving the cell's preparation for DNA replication. Dysregulation of cyclin E is commonly associated with cancer, highlighting its significance in gene regulation and cellular proliferation.
Cyclin-dependent kinases: Cyclin-dependent kinases (CDKs) are a family of protein kinases that play a crucial role in regulating the cell cycle by phosphorylating specific target proteins when activated by binding to cyclins. This interaction is vital for the progression through different phases of the cell cycle, including DNA replication and mitosis, making them key players in cellular division and growth.
Cyclins: Cyclins are proteins that regulate the progression of the cell cycle by activating cyclin-dependent kinases (CDKs). They ensure that cell cycle events occur in the correct sequence and at the appropriate time.
Cyclins: Cyclins are a family of proteins that play a crucial role in regulating the cell cycle by activating cyclin-dependent kinases (CDKs). These proteins are essential for transitioning between different phases of the cell cycle, ensuring that cellular processes such as DNA replication and cell division occur in a timely and orderly manner. Cyclins are synthesized and degraded in a cyclical pattern, reflecting their name, which is critical for the precise control of cell division.
DNA methylation: DNA methylation is a biochemical process involving the addition of a methyl group to the DNA molecule, typically at cytosine bases in the context of CpG dinucleotides. This modification plays a critical role in regulating gene expression by influencing chromatin structure and accessibility, impacting how genes are turned on or off. Through this mechanism, DNA methylation contributes significantly to cellular differentiation, development, and the stability of the genome.
DNA methyltransferase inhibitors: DNA methyltransferase inhibitors are compounds that block the activity of DNA methyltransferases, enzymes responsible for adding methyl groups to DNA, which can affect gene expression and cellular function. These inhibitors play a crucial role in cancer treatment by reversing abnormal gene silencing that is often associated with tumorigenesis. By demethylating DNA, they can restore the expression of tumor suppressor genes, thereby helping to halt or reverse cancer progression.
EGFR: EGFR, or Epidermal Growth Factor Receptor, is a cell surface receptor that, when activated by its ligands, triggers a cascade of signaling pathways involved in cell proliferation, survival, and differentiation. This receptor plays a crucial role in normal cellular processes, but when mutated or overexpressed, it is often implicated in various cancers, making it a key focus in cancer research and targeted therapies.
HER2: HER2, or Human Epidermal Growth Factor Receptor 2, is a protein that promotes cell growth and division. In the context of cancer, HER2 is often overexpressed in certain types of breast cancer, leading to aggressive tumor growth. This overexpression is linked to disruptions in normal cell signaling pathways and has significant implications for targeted therapies.
Histone Deacetylase Inhibitors: Histone deacetylase inhibitors (HDAC inhibitors) are a class of compounds that block the activity of histone deacetylases, enzymes responsible for removing acetyl groups from histones, leading to changes in gene expression. By inhibiting these enzymes, HDAC inhibitors can reactivate silenced genes, which is particularly significant in the context of cancer, where many tumor suppressor genes are often turned off. These compounds play a crucial role in epigenetic regulation, influencing cell differentiation and proliferation.
Histone modifications: Histone modifications are chemical alterations to the histone proteins around which DNA is wrapped, influencing gene expression by altering chromatin structure and accessibility. These modifications play a crucial role in regulating epigenetic processes, impacting cellular functions and identity, and are linked to important biological phenomena such as development and disease.
Imatinib: Imatinib is a targeted therapy drug used primarily to treat certain types of cancer, particularly chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). It works by inhibiting specific tyrosine kinases, which are enzymes that play a key role in the signaling pathways that regulate cell division and survival. By blocking these signals, imatinib effectively halts the growth of cancer cells, highlighting its importance in cancer treatment and gene regulation.
Kinase inhibitors: Kinase inhibitors are a class of small molecules or compounds that block the action of kinases, enzymes that add phosphate groups to proteins and play a crucial role in regulating various cellular processes. By inhibiting these enzymes, kinase inhibitors can disrupt signaling pathways that are often altered in cancer cells, making them vital in cancer treatment as they target specific molecular abnormalities.
Li-Fraumeni syndrome: Li-Fraumeni syndrome is a rare inherited disorder characterized by a heightened risk of developing various types of cancer, particularly in children and young adults. This syndrome is linked to mutations in the TP53 gene, which plays a crucial role in regulating the cell cycle and maintaining genomic stability, making it an important player in cancer prevention and gene regulation.
Metastasis: Metastasis is the process by which cancer cells spread from the original (primary) tumor to distant sites in the body, forming secondary tumors. This process is a key feature of cancer progression, as it enables cancer to invade tissues and organs beyond the initial site, making treatment more complex and challenging. Metastasis involves several steps, including local invasion, entry into the bloodstream or lymphatic system, survival in circulation, and colonization at new sites.
Methylation: Methylation is a biochemical process involving the addition of a methyl group (-CH₃) to DNA, which can influence gene expression without altering the DNA sequence. This process plays a critical role in regulating gene activity, affecting cellular functions such as growth, development, and differentiation. In addition, methylation patterns can be heritable and are crucial for maintaining cellular identity and function.
Monoclonal antibodies: Monoclonal antibodies are laboratory-made molecules engineered to serve as substitute antibodies that can enhance, mimic, or inhibit the immune system's attack on target cells. These specialized proteins are produced by identical immune cells cloned from a unique parent cell, allowing them to bind specifically to certain antigens. They play a vital role in diagnostics, therapeutics, and research, particularly in areas like cancer treatment, biotechnology applications, viral infection management, and understanding the immune response.
Myc: Myc is a family of regulator genes and proteins that play a critical role in cell cycle progression, apoptosis, and cellular transformation. These genes encode transcription factors that help control the expression of various genes involved in cell growth and proliferation, making Myc a significant player in cancer development when dysregulated.
Oncogenes: Oncogenes are mutated forms of normal genes, known as proto-oncogenes, that drive the growth and proliferation of cancer cells. They play a critical role in the development of cancer by promoting uncontrolled cell division, often by encoding proteins that stimulate cell cycle progression or inhibit apoptosis. The activation of oncogenes can be caused by various factors, including genetic mutations, chromosomal rearrangements, and viral infections.
P21: p21 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating the cell cycle, specifically functioning as a checkpoint that can halt the progression of cells through the cycle in response to DNA damage or stress signals. By inhibiting cyclin-CDK complexes, p21 helps maintain genomic stability and prevent the uncontrolled cell division that characterizes cancer. Its expression is often regulated by the tumor suppressor protein p53, linking it to both normal cellular function and cancer biology.
P27: p27 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating the cell cycle by inhibiting the activity of cyclin-CDK complexes, particularly in the transition from G1 to S phase. By controlling the progression of the cell cycle, p27 ensures that cells do not divide uncontrollably, linking its function to both normal cellular processes and cancer development.
P53: p53 is a crucial tumor suppressor protein that regulates the cell cycle and helps maintain genomic stability by preventing the proliferation of cells with damaged DNA. It plays a significant role in the control of cell growth, ensuring that cells do not divide uncontrollably, which is particularly important in the context of cancer development and gene regulation.
Proto-oncogenes: Proto-oncogenes are normal genes that play essential roles in cell growth, differentiation, and division. When mutated or abnormally expressed, these genes can become oncogenes, which contribute to the development of cancer by promoting uncontrolled cell proliferation. Understanding proto-oncogenes is crucial as they are key players in the regulation of the cell cycle and can influence cancer progression and gene regulation.
PSA: Prostate-specific antigen (PSA) is a protein produced by the prostate gland, primarily found in semen, but also present in small amounts in the blood. Its measurement is a critical tool in the diagnosis and management of prostate cancer, as elevated levels can indicate the presence of cancer or other prostate disorders. Understanding PSA levels helps guide treatment decisions and monitor disease progression.
Ras: Ras is a family of small GTPase proteins that play a crucial role in transmitting signals within cells, particularly in the regulation of cell growth and differentiation. These proteins act as molecular switches that toggle between an active GTP-bound state and an inactive GDP-bound state, influencing key pathways involved in the cell cycle and cell signaling, making them integral to understanding processes like cell division and cancer development.
RB: RB, or retinoblastoma protein, is a crucial tumor suppressor that plays a significant role in regulating the cell cycle. It controls the transition from the G1 phase to the S phase, preventing excessive cell growth and division. When functional, RB binds to and inhibits transcription factors that promote cell cycle progression, ensuring that cells do not proliferate uncontrollably, which is a key aspect of cancer development.
Telomerase: Telomerase is an enzyme that adds repetitive nucleotide sequences to the ends of chromosomes, known as telomeres, thus preventing chromosome deterioration during DNA replication. This enzyme plays a crucial role in maintaining genomic stability, particularly in stem cells and cancer cells, where it allows for continuous cell division without losing important genetic information.
Trastuzumab: Trastuzumab is a monoclonal antibody used primarily to treat breast cancer that is overexpressing the HER2 protein. By binding to the HER2 receptor on cancer cells, trastuzumab blocks their growth and survival signals, making it an essential tool in targeted cancer therapy. This targeted approach highlights the role of gene regulation in cancer, as HER2 is encoded by a gene that, when amplified, can lead to aggressive tumor behavior.
Tumor microenvironment: The tumor microenvironment refers to the complex and dynamic ecosystem surrounding a tumor, which includes various cell types, extracellular matrix components, blood vessels, and signaling molecules. This environment plays a crucial role in cancer development and progression, influencing how cancer cells grow, invade, and respond to treatment. Understanding the tumor microenvironment is essential for uncovering the mechanisms of cancer gene regulation and developing more effective therapies.
Tumor suppressors: Tumor suppressors are genes that help regulate cell growth and division, acting as safeguards against uncontrolled cell proliferation that can lead to cancer. These genes produce proteins that can repair DNA, control the cell cycle, and initiate apoptosis (programmed cell death) when necessary. When tumor suppressor genes are mutated or inactivated, their protective functions are lost, increasing the risk of cancer development.
Vorinostat: Vorinostat is a histone deacetylase inhibitor (HDACi) that is primarily used as a treatment for certain types of cancer, particularly cutaneous T-cell lymphoma (CTCL). By inhibiting histone deacetylases, vorinostat alters gene expression and promotes cell cycle arrest and apoptosis in cancer cells, making it an important tool in the context of cancer therapy and gene regulation.