Lecture 19

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Questions and Answers

What is the fundamental principle that lies at the heart of carcinogenesis?

Non-lethal genetic damage (correct)

Accumulation of mutations over time

Viral infections only

Environmental agents only

What type of mutations confer a growth advantage on cells?

Driver mutations (correct)

Passenger mutations

Proto-oncogenes

Oncoproteins

What is a characteristic of normal cells in terms of growth factors?

Uncontrolled proliferation

Independence from growth factors

Dependence on growth factors (correct)

Sensitivity to apoptosis

What happens to normal somatic cells after a limited number of divisions?

They enter senescence Signup and view all the answers

What is a characteristic of oncogenes?

They promote uncontrolled cell growth autonomously Signup and view all the answers

What is a hallmark of cancer?

Sustaining proliferative signaling Signup and view all the answers

What is a mechanism of self-sufficiency in growth signals in cancer cells?

Stimulus-independent secretion of growth factor Signup and view all the answers

What is the result of the accumulation of mutations over time in a cell?

Development of a malignant tumor Signup and view all the answers

What is the function of tumor suppressor genes?

To inhibit cellular proliferation by regulating the cell cycle Signup and view all the answers

What is the term for the normal genes that promote cell proliferation and differentiation?

Proto-oncogenes Signup and view all the answers

What is the result of mutations in cyclin genes?

Uncontrolled cell proliferation Signup and view all the answers

What is the function of the RAS gene?

To encode signaling proteins from receptor to nucleus Signup and view all the answers

What is the result of overexpressing nuclear transcription factors?

Promoting cell cycle progression Signup and view all the answers

What is the result of mutations in the Her2/NEU receptor?

Uncontrolled cell proliferation Signup and view all the answers

What is the result of the BCR-ABL fusion gene?

Growth autonomy and impaired apoptosis Signup and view all the answers

What is the function of the MYC gene?

To promote cell cycle progression Signup and view all the answers

What is the characteristic of tumor suppressor genes in terms of carcinogenesis?

Both copies of the gene must be lost Signup and view all the answers

What is the result of inheriting one defective copy of a tumor suppressor gene and losing the second one through somatic mutation?

Familial predisposition for tumor development Signup and view all the answers

What is the role of the RB gene in retinoblastoma?

It causes both alleles to be lost Signup and view all the answers

Why does familial transmission of retinoblastoma follow an autosomal dominant inheritance pattern?

Because only one somatic mutation is required for expression of the disease Signup and view all the answers

What is the role of the TP53 gene?

It senses DNA damage and assists in DNA repair Signup and view all the answers

What is the result of activating the DNA damage checkpoint?

The cell cycle is arrested and DNA repair or apoptosis occurs Signup and view all the answers

What is the role of the APC gene?

It is a tumor suppressor gene lost in Adenomatous polyposis coli Signup and view all the answers

What is the result of P53 inducing DNA repair genes?

The cell cycle is arrested Signup and view all the answers

Study Notes

The Molecular Basis of Cancer

Oncogenesis is the formation or induction of tumors, involving mutant forms of normal genes called proto-oncogenes, which code for oncoproteins.
Genetic damage, acquired through environmental agents or inherited, is the fundamental principle of carcinogenesis, resulting in a single progenitor cell that has incurred genetic damage and undergoes clonal expansion.
Carcinogenesis involves the accumulation of mutations over time, as well as one-off catastrophic events.

Mutations in Cancer

Driver mutations confer a growth advantage on cells and are located in cancer genes.
Passenger mutations do not confer a growth advantage.

Normal Cellular Processes

Dependence on growth factors and cell/tissue-specific signals is a normal characteristic of cells.
Loss of these signals leads to apoptosis.
Anchorage-dependent proliferation requires interaction with the extracellular matrix (ECM) through transmembrane proteins (integrins).
Contact inhibition occurs when cells are in contact with each other, inhibiting proliferation and movement.
Normal somatic cells have a limited number of divisions before entering senescence.

The Hallmarks of Cancer

Sustaining proliferative signaling: oncogenes promote uncontrolled cell proliferation through mechanisms such as stimulating independent growth factor secretion, mutated growth factor receptors, and over-expressed nuclear transcription factors.

Oncogenes and Tumor Suppressor Genes

Oncogenes are mutated forms of proto-oncogenes that promote cancer cell growth autonomously.
Oncoproteins (products of oncogenes) promote uncontrolled cell proliferation.
Mechanisms of self-sufficiency in growth signals include:
- Stimulus-independent secretion of growth factors
- Mutation/over-expression of growth factor receptors
- Mutation in genes encoding signaling proteins from receptor to nucleus
- Over-expression of nuclear transcription factors promoting cell cycle
- Mutations in cyclin genes resulting in uncontrolled cell proliferation
Tumor suppressor genes encode proteins that inhibit cellular proliferation by regulating the cell cycle.
Mutation in tumor suppressor genes leads to uninhibited cell proliferation.

Tumor Suppressor Genes

Both copies of the gene must be lost for carcinogenesis to occur (autosomal recessive).
In cases with familial predisposition, affected persons inherit one defective copy of a tumor suppressor gene and lose the second one through somatic mutation.
Examples of tumor suppressor genes include:
- RB gene in retinoblastoma
- P53 in human cancers
- APC in Adenomatous polyposis coli

Cell Cycle Regulation

The RB gene prepares for mitosis and controls the cell cycle.
DNA damage checkpoint arrests the cell cycle, allowing for DNA repair or apoptosis.
P53 is a tumor suppressor gene that maintains the integrity of the genome and senses DNA damage, assisting in DNA repair by arresting the cell cycle and inducing DNA repair genes.