Cancer Biology: Oncogenes and Tumor Suppressors

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Questions and Answers

What effect does a point mutation in Ras oncogenes have on the Ras protein?

It has no effect on the Ras protein.

It allows the Ras protein to shut itself off.

It makes the Ras protein inactive.

It causes the Ras protein to become hyperactive. (correct)

Which of the following statements about the p53 gene is true?

It is commonly mutated in human cancers. (correct)

It only regulates the apoptosis pathway.

It has no role in genetic stability.

It functions primarily in cell metabolism.

What is the characteristic feature of cancer cells that leads to a second mutation?

Enhanced apoptosis.

Improved DNA repair mechanisms.

Hypermutability. (correct)

Reduced proliferation rates.

Which of the following roles does the p53 gene NOT have?

Enhancing oncogenic signaling. Signup and view all the answers

How does the Ras protein mutation affect external stimulus requirements for cell proliferation?

It makes external mitogen signals irrelevant. Signup and view all the answers

What is the primary role of proto-oncogenes in the cell cycle?

To code for proteins required for normal cell proliferation Signup and view all the answers

How is a dominant mutation characterized in cancer-critical genes?

Only one mutated copy is needed for a phenotypic change Signup and view all the answers

What type of mutations inactivate tumor suppressor genes?

Mutations that cause gene inactivation Signup and view all the answers

What characterizes oncogenes in relation to proto-oncogenes?

They arise from mutations in proto-oncogenes, leading to excessive proliferation Signup and view all the answers

What is one way that gene activation of a proto-oncogene can lead to cancer?

Through alteration of the protein coding sequence or regulatory regions Signup and view all the answers

What is the primary reason cancer incidence increases with age?

Accumulation of random mutations over time. Signup and view all the answers

What is the importance of clonal evolution in cancer?

It allows for the natural selection of cells with advantageous mutations. Signup and view all the answers

At least how many mutations must accumulate to transform normal cells into cancer cells?

5 Signup and view all the answers

What characteristic is NOT typical of cancer cells?

Dependence on neighboring cells for survival Signup and view all the answers

What is a key factor contributing to genetic instability in cancer cells?

Defective DNA repair mechanisms Signup and view all the answers

How do cancer stem cells contribute to tumor development?

They are capable of unlimited division and can give rise to cancer. Signup and view all the answers

What happens to cancer cells with respect to cell senescence?

They divide indefinitely by avoiding normal senescence. Signup and view all the answers

What is the role of apoptosis in the context of cancer cell progression?

It reduces cell division rates, aiding cancer progression. Signup and view all the answers

What is a common mutation found in cancer cells?

Mutations in DNA maintenance genes Signup and view all the answers

What defines the process of tumor progression?

A multi-step accumulation of mutations over years. Signup and view all the answers

What is the primary behavior characteristic of cancer cells?

Selfish non-cooperative behavior Signup and view all the answers

What initiates the potential for cancer development in cells?

Failure of somatic mutation repair Signup and view all the answers

Which type of cancer arises from epithelial cells?

Carcinomas Signup and view all the answers

What are benign tumors characterized by?

Non-cancerous nature Signup and view all the answers

Which of the following statements about somatic mutations is true?

Somatic mutations happen in body cells. Signup and view all the answers

What is a key trait of malignant tumors?

Ability to metastasize Signup and view all the answers

Over time, how does cancer typically develop?

Through repeated rounds of mutation and selection Signup and view all the answers

What type of cancer arises from cells of the nervous system?

Neoplastic neuromas Signup and view all the answers

Which statement best describes hyperplasia in cancerous cells?

Cells increase excessively in number Signup and view all the answers

What may lead to a selective advantage in cancer cells?

Mutations allowing faster growth and division Signup and view all the answers

What is the primary function of the p53 tumor suppressor gene?

To act as a cellular stress sensor Signup and view all the answers

What happens to cells that are defective in p53?

They fail to respond to stress appropriately Signup and view all the answers

Why do at least 5 mutations need to accumulate for cancer to develop?

Because of complex regulatory mechanisms in multicellular organisms Signup and view all the answers

Which gene mutation is identified as a central ingredient for the development of colorectal cancer?

APC Signup and view all the answers

What characteristic do cells lose when the APC gene is mutated?

Cell-cell adhesion properties Signup and view all the answers

Most human cancers contain mutations in which of the following genes?

p53, Ras, and Rb Signup and view all the answers

Why do different colorectal cancer patients have different combinations of mutations?

Different cell abnormalities Signup and view all the answers

What is a recommended strategy for cancer prevention?

Avoid known carcinogens Signup and view all the answers

What is a key factor for successful outcomes in cancer treatment?

Early and precise diagnosis Signup and view all the answers

What is a characteristic of traditional cancer treatments?

They damage DNA to induce apoptosis in cancer cells Signup and view all the answers

Why do tumors develop resistance to cancer drugs?

Tumors are constantly mutating and evolving Signup and view all the answers

What is the advantage of administering two drugs simultaneously in treating tumors?

It makes it highly improbable for cells to gain resistance Signup and view all the answers

What is a goal of new cancer therapies?

To exploit specific molecular abnormalities of cancer cells Signup and view all the answers

How does the drug Gleevec work against cancer cells?

It binds to mutated tyrosine kinase, inhibiting proliferation Signup and view all the answers

What type of cancer typically has an earlier average age of onset?

Leukemias Signup and view all the answers

After exposure to a carcinogen, what delay is often observed before cancer develops?

10-20+ years Signup and view all the answers

Study Notes

Cancer Overview

Multi-cellular organisms function as a society or ecosystem, where self-sacrifice (collaboration) outweighs survival of the fittest.
Molecular disturbances disrupt this harmony, causing issues in multi-cellular societies.
Cancer is a suitable topic to conclude a cellular and molecular biology course. It's an outcome of malfunctioning regulatory mechanisms in cells' normal behaviors when cells become non-cooperative or "selfish."

Cancer as Microevolution

The human body contains more than 10¹³ cells, experiencing billions of mutations daily.
DNA replication is highly accurate, but some mutations evade cell repair.
Most genes likely experience mutations more than 10⁹ times per individual.
The problematic aspects of cancer are not why mutations occur, but rather their infrequent occurrence.
A mutation can provide a cell with an advantage to grow, divide, and outcompete neighbors, forming a mutated clone.
This "selfish" behavior jeopardizes the overall organism's health.
Mutation, competition, and natural selection, within a population of cells, can lead to malignant cancer.

Main Cancer Types

Over 200 types of cancer are classified into four main categories.
Carcinomas (~30% of human cancers) originate from epithelial cells.
Sarcomas (rare in humans) arise from connective tissue (like bone, cartilage, and muscle).
Leukemias/lymphomas originate from blood cells (hemopoietic cells).
Neoplastic neuromas derive from nervous system cells (neurons and neuroglia).

Major Cancer Traits

Hyperplasia: Excessive growth and proliferation of cells that form tumors.
Metastasis: Cancer cells detach, travel through blood/lymphatics, and form secondary tumors (metastases).
Benign tumors do not metastasize. Malignant tumors are cancerous.

Cancer Development & Factors

Cancer develops through an accumulation of somatic mutations (not germline).
The mutations must be inheritable, meaning they pass to progeny.
Cells can have genetic or epigenetic changes (e.g., DNA sequence mutations or alterations in gene expression without DNA changes).
Cancer requires multiple steps/mutations to develop over many years.
Individuals with DNA repair defects accumulate mutations at a faster rate.

Cancer Cell Characteristics

Genetically unstable: Exhibit increased mutation rates due to replication/repair/segregation errors.
Defective control: Lose dependence on signals for survival, death, and differentiation.
Abnormally invasive: Lack adhesion molecules, survive in unusual places, and secrete enzymes that break down the extracellular matrix (ECM).
Absence of senescence: Cells proliferate indefinitely.
Resistance to DNA damage: Display altered responses to DNA damage and stress.
Heterogeneous: Tumors are made up of different clones with diverse combinations of mutations.

Cancer Cells - Unstable Genetics

Cancer cells accumulate genetic changes at accelerated rates.
Some cells struggle to repair DNA damage or regulate chromosome integrity.
Genetic mutations may occur in DNA maintenance genes.
Karyotypes show abnormalities in cancerous cells.

Factors Contributing to Instability

Defects in DNA replication/repair.
Defects in cell-cycle checkpoints.
Mistakes during mitosis.
Abnormal chromosome numbers.

Increased Cell Division/Apoptosis' Effect

Increased cell division and decreased apoptosis increase the number of cells, thus increasing the potential for mutations.

Cancer Stem Cells

Specialized cells, typically unable to divide, need constant replacement.
Stem cells (precursors) generate replacement cells.
Cancer stem cells arise from normal stem cells or differentiated cells, contributing to unlimited cell division.

Absence of Cell Senescence

Normal cells have a limit on cell divisions before apoptosis starts.
Telomere shortening triggers apoptosis in normal cells.
Cancer cells overcome senescence by maintaining telomerase activity or changing cell cycle control pathways (e.g., failing to activate p53 pathway).

Steps in Metastasis

Cells grow benignly in epithelial tissue.
Cells become invasive and enter capillaries.
Cancer cells travel via bloodstream, escaping blood vessels.
Colonization of new sites (liver, etc.) for metastatic growth.

Two Types of Cancer Genes

Proto-oncogenes: Code for proteins that promote normal cell proliferation.
Mutant oncogenes: Become overactive, encouraging excessive proliferation (e.g., mutations on Ras, B-catenin).
Tumor suppressor genes: Code for proteins that inhibit cell proliferation.
Loss-of-function mutations on tumor suppressor genes lead to unchecked proliferation.

Oncogenes and Tumor Suppressors

Proto-oncogenes can cause oncogenes by acquiring gain-of-function mutations.
Tumor suppressor genes often need both copies to inactivate to cause cancer.

Converting Proto-oncogenes to Oncogenes

Mutations in coding sequences, gene amplification, or chromosomal rearrangements can convert proto-oncogenes to oncogenes.
Overactive oncogenes drive continuous cell proliferation even without signals.

Loss of Tumor Suppressor Gene Function

Losing tumor suppressor gene function often involves both genetic and epigenetic changes.
p53 is an important tumor suppressor gene in cell cycle-regulation, apoptosis, and DNA damage-repair.
Mutations in many pathways result from p53 loss.

Why multiple mutations are needed for cancer development

Complex regulatory systems and redundant backup processes prevent unchecked cell growth.
Many regulatory systems must be impaired before a cell loses normal restraints and behaves as a cancer cell.

Development of Colorectal Cancer

At least 5 mutations are needed in a lineage of cells for cancer development.
APC is a crucial gene for colorectal cancer development.
Cells lose cell-cell adhesion abilities and gain stem cell traits.
Multiple mutations in p53, Ras, and Rb are involved.

Different Colorectal Cancer Patients

Different colorectal cancer patients will have different combinations/mutations.
Diversity in mutations impacts treatment response.

Current Cancer Treatments

Prevention: Avoidance of known carcinogens.
Early detection: Diagnostic tools like pap smears, mammograms.
Treatments: Surgery, radiation, chemotherapy, immunotherapy, and gene therapy.
Many treatments target cancer cells by damaging DNA leading to their death or halting their proliferation.
Multidrug Treatments: Simultaneous use of multiple drugs may reduce tumor resistance, as it is highly improbable for tumors to develop resistance simultanesouly to two different drugs.

New Cancer Therapies

Custom treatments: Tailored to the specific changes in a patient's cancer cells.
Targeting mutated proteins: Inactivation of cancerous proteins without affecting normal cell function.

At-Home Exercises

Leukemia, early-onset cancer - explanation for earlier onset needs provided
Heavy smokers, industrial workers, delayed cancer onset - explanation for delayed progression needs provided
Is cancer hereditary? - Explanation needs provided
Choosing targets for cancer therapies (oncogenes vs. tumor suppressor genes) - explanation needs provided

iClicker Questions

Malignant vs. Benign Tumors: Malignant cells invade other tissues.
Converting Proto-oncogenes: Specific mutations, gene amplification, chromosomal rearrangements can turn proto-oncogenes to oncogenes, or causing the normal protein to be overproduced.
False Statement About Mutations in Cancer - APC is a tumor suppressor, not a proto-oncogene

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Description

This quiz delves into key concepts related to oncogenes and tumor suppressor genes, focusing on the roles of Ras and p53 proteins in cancer development. Answer questions about mutations, their effects on cell proliferation, and the characteristics of proto-oncogenes. Perfect for students studying cancer biology or genetics.