Oncogenes and Cancer Development

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Questions and Answers

What are oncogenes derived from?

Apoptotic genes

Normal cellular processes

Tumor suppressor genes

Mutated proto-oncogenes (correct)

Which of the following processes can lead to the activation of oncogenes?

Gene deletion

Point mutations (correct)

Cellular differentiation

RNA splicing

What effect does autocrine stimulation have on tumor cells?

It inhibits cell division.

It drives abnormal cell proliferation. (correct)

It causes cells to enter apoptosis.

It normalizes cell growth.

Which of the following is NOT a well-known oncogene?

P53 Signup and view all the answers

What typically happens to growth factor receptors in relation to oncogenes?

They are converted to oncogene proteins through alterations. Signup and view all the answers

How do oncogenes contribute to cancer development?

They stimulate continuous cell growth and division. Signup and view all the answers

What is a consequence of gene amplification in oncogene activation?

Increased production of growth-stimulating proteins. Signup and view all the answers

Which oncogene alteration involves a reorganization of DNA?

Chromosomal translocation Signup and view all the answers

What is one way in which oncogenes contribute to tumor formation?

By promoting excessive cell division Signup and view all the answers

What process allows cancer cells to spread to other body parts?

Altered cellular movement Signup and view all the answers

What is a characteristic feature of tumors derived from single cells?

Uniform expression of alleles Signup and view all the answers

How does X chromosome inactivation relate to cancer tumor characterization?

It shows a fixed pattern of allele expression Signup and view all the answers

What is one clinical application of studying oncogenes?

Creating diagnostic markers for specific cancers Signup and view all the answers

What role do oncogenes play in the process of angiogenesis?

They promote blood vessel formation to sustain tumors Signup and view all the answers

What is the effect of the Tel/PDGFR fusion protein on the PDGF receptor?

It leads to constitutive activity of the intracellular kinase domain. Signup and view all the answers

Which of the following factors is increased due to certain oncogenes, leading to genomic instability?

Likelihood of additional mutations Signup and view all the answers

What are the three genetic mechanisms that activate oncogenes in human neoplasms?

Mutation, gene amplification, and chromosome rearrangements Signup and view all the answers

How is the expression of alleles typically observed in normal tissues compared to tumor tissues?

Normal tissues have mixed allele expression. Signup and view all the answers

How can erbB-2 be activated as an oncogene?

By gene amplification. Signup and view all the answers

What is the consequence of genetic alterations that activate oncogenes?

A survival advantage for the cell Signup and view all the answers

What role do Ras proteins play in cellular signaling?

They couple growth factor receptors to Raf activation. Signup and view all the answers

Which of the following best describes gene amplification?

An increase in gene copy number within a cell's genome Signup and view all the answers

What is the consequence of deletions in the raf gene?

Loss of the amino-terminal regulatory domain. Signup and view all the answers

Which types of mutations are most commonly associated with oncogene activation in human tumors?

Base substitutions (point mutations) Signup and view all the answers

What are double-minute chromosomes (DMs)?

Minichromosome structures without centromeres Signup and view all the answers

Which transcription factors are components of the AP-1 complex?

Fos and Jun. Signup and view all the answers

What role do tumor suppressor genes play in neoplasia?

They help maintain normal cell function. Signup and view all the answers

What is the role of the ERK MAP kinase in gene expression?

To induce transcription of proto-oncogenes. Signup and view all the answers

What is the effect of unregulated expression of Fos or Jun proteins?

It drives abnormal cell proliferation. Signup and view all the answers

What is a feature of homogeneous staining regions (HSRs)?

They lack a normal alternating pattern of light- and dark-staining bands. Signup and view all the answers

How do Myc proteins contribute to cancer development?

By functioning as transcription factors regulated by growth stimuli. Signup and view all the answers

Which of the following best describes the relationship between protooncogenes and tumor suppressor genes in cancer development?

Protooncogene activation usually occurs alongside tumor suppressor gene loss. Signup and view all the answers

Study Notes

Oncogenes

Oncogenes are mutated or overexpressed versions of normal cellular genes, also known as proto-oncogenes.
Proto-oncogenes regulate essential cellular processes, such as growth, proliferation, and survival.
Under normal conditions, proto-oncogenes help control cell division and differentiation.
Oncogenes drive continuous cell growth and division, overriding normal regulatory mechanisms.
Activation of oncogenes is a crucial step in cancer development.
Oncogenes can be activated through various processes, including point mutations (a single DNA change), gene amplification (increasing gene copies), and chromosomal translocations (rearranging DNA).
Oncogenes such as RAS, MYC, and HER2/neu play roles in cell growth and regulation.
Growth factors, acting as oncogenes, result from abnormal expression, self-stimulating growth factor production, ultimately causing abnormal cell proliferation in tumor development.
Growth factor receptors, encoded by oncogenes, such as protein tyrosine kinases, can be altered activating oncogene proteins.
Some examples include the PDGF receptor activation by chromosome translocations featuring transcription factor sequences.
Additional oncogenes such as erbB-2 and others encode non-receptor protein-tyrosine kinases activated by mutations or deletions of regulatory sequences.
Ras proteins play a key role in mitogenic signaling by coupling growth factor receptors to Raf protein kinase, which activates ERK MAP kinase.
Raf genes, similarly, can be converted to oncogenes by deletions affecting their regulatory domains, leading to unregulated protein kinase and MAP kinase activation.
Transcription factors like Fos and Jun, components of the AP-1 transcription factor, respond to growth factor-induced transcription in stimulated cells.
Myc transcription factors are regulated by mitogenic stimuli and their abnormal expression can contribute to tumor development.
Oncogenes, activated through various chromosome translocations, are involved in leukemias and lymphomas.

Mechanisms of Oncogene Activation

Oncogene activation is facilitated by genetic changes to proto-oncogenes leading to growth advantage for the cell.
Three primary mechanisms are responsible: mutations, gene amplification, and chromosome rearrangements.
These mechanisms either alter proto-oncogene structure or increase expression, contributing to tumor development.
Typically, multiple cancer-associated gene alterations are involved in full expression of a tumor's phenotype including its capacity for metastasis. Proto-oncogene activation and tumor suppressor gene loss or inactivation are often involved.

Types of Oncogene Mutations

Mutations can affect critical protein regulatory regions, often causing uncontrolled activity of the mutated protein.
Mutations can include base substitutions, deletions, and insertions.
Retroviral oncogenes frequently exhibit deletions contributing to activation.
Examples of mutation effects include alterations in the amino-terminal ligand-binding domains of oncogenes like erbB, kit, ros, met, and trk.
Most characterized oncogene mutations, commonly referred to as point mutations, involve single amino acid changes within the protein.

Gene Amplification

Gene amplification represents an increase in the copy number of a gene within a cell's genome.
This mechanism is a crucial factor for tumor cells to develop resistance to anti-tumor drugs.
The process involves repetitive replication of genomic DNA generating karyotypic abnormalities like double-minute chromosomes (DMs) and homogeneous staining regions (HSRs).
Large regions of amplified genomic DNA, often encompassing numerous copies of a gene, are associated with increased gene expression, conferring a selective advantage for cell growth.

Significance in Cancer Development

Oncogenes are central to cancer development and progression.
They promote tumor formation by increasing cell division.
Oncogenes affect cell adhesion and movement, facilitating metastasis.
Activation of oncogenes triggers blood vessel formation (angiogenesis) supporting tumor sustenance and nutrient/oxygen supply.
Some oncogenes induce genomic instability, increasing mutation probability, further fueling genetic chaos within cancer cells.
Tumor clonality, a key feature of cancer, involves the proliferation of a single cell's aberrant growth. X-chromosome inactivation is involved in tumor clonality studies.
During embryonic development, one X chromosome within female cells is inactivated by being converted to heterochromatin. This process can influence the expression of specific genes on that chromosome in distinct cells, hence explaining the use of X-chromosome inactivation analysis.

Clinical Implications

Oncogene studies have significantly advanced cancer diagnosis and treatment strategies.
Diagnostic markers, like HER2, are used to diagnose cancer types and predict prognosis.
Understanding oncogenes facilitates the development of targeted therapies.
Drugs like trastuzumab target specific oncogenes such as HER2 in breast cancer, while imatinib targets the BCR-ABL fusion protein in chronic myeloid leukemia.
Despite advancements, cancers can develop resistance to these treatments, emphasizing the need for combination therapies and further research.

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Description

This quiz explores the concept of oncogenes, which are mutated or overexpressed versions of proto-oncogenes that play a critical role in cancer development. It discusses how these genes regulate cell growth, proliferation, and the mechanisms through which they become activated. Understand the significance of various oncogenes such as RAS, MYC, and HER2/neu in the context of tumor development.