Biology of Cancer

A.M. FORENTIN., M.SI., APT.

 What is cancer?
Abnormal cell growth (neoplasia)
Malignant as opposed to benign
◦ Benign: slow growth, non-invasive, no metastasis
◦ Malignant: rapid growth, invasive, potential for metastasis
Hallmarks of cancer
 What types of genes get mutated in cancer?

Oncogenes are activated

◦ Normal function: cell growth, gene transcription
Tumor suppressor genes are inactivated
◦ Normal function: DNA repair, cell cycle control, cell death

Mutator Genes
◦ Genes whose products ensure accurate DNA replication and DNA repair
Mutagens
Viruses: insertional mutagenesis

Chemicals: DNA adducts

UV and ionizing radiation: single and

double strand DNA breaks
 Oncogenes
All are involved in positive control of cell growth and division.
◦ About 100 different oncogenes have been identified

Can be various kinds of proteins:

◦ Growth factors, regulatory genes involved in the control of cell multiplication.
◦ Protein kinases, add phosphate groups to target proteins, important in signal transduction
pathways.

“Proto-oncogenes”
◦ Normal form of the gene that is involved in positive regulation of the cell cycle
 Oncogenes
A few cancer syndromes are caused by inherited mutations of proto-oncogenes that cause the
oncogene to be turned on (activated). But most cancer-causing mutations involving oncogenes
are acquired, not inherited.

They generally activate oncogenes by:

o Chromosome rearrangements: Changes in chromosomes that put one gene next to another,
which allows one gene to activate the other

o Gene duplication: Having extra copies of a gene, which can lead to it making too much of a
certain protein
 Tumor suppressors

• “Guardian(s) of the genome”

• Often involved in maintaining genomic integrity (DNA repair,
chromosome segregation)
• Mutations in tumor suppressor genes lead to the “mutator
phenotype”—mutation rates increase
 Tumor Suppressor Genes
Normally inhibit cell growth
Example: retinoblastoma
◦ RB protein normally blocks a
transcription factor, E2F
 Rb—a classic tumor suppressor

• Rb binds to a protein called E2F1

• E2F1 initiates the G1/S cell cycle transition
• When bound to Rb, E2F1 can't function
• Thus, Rb is a crucial cell cycle checkpoint
 RB1
• RB1 gene provides instructions for making a protein called pRB.
• RB1 is a tumor suppressor gene, which means that it normally
regulates cell growth and stops cells from dividing too rapidly or in an
uncontrolled way.
• Mutations in the RB1 gene are responsible for most cases
of retinoblastoma

https://ghr.nlm.nih.gov/condition/retinoblastoma
A small percentage of retinoblastomas are caused by deletions in the region of
chromosome 13 that contains the RB1 gene
 p53—a classic tumor suppressor

• “The guardian angel of the genome”

• Senses genomic damage
• Halts the cell cycle and initiates DNA
repair
• If the DNA is irreparable, p53 will initiate
the cell death process
 p53 Gene
Detects DNA damage
The “Last Gatekeeper”
◦ Involved in 50% of cancers
◦ Often not malignant despite other cancer-causing mutations until p53 is
inactivated by mutation.
Two possible responses to DNA damage:
◦ 1) Acts as a Transcription Factor to activate expression of p21, which inhibits
CDK/G1 cyclin to halt the cell cycle; then activates DNA repair.
◦ 2) Triggers Apoptosis (programmed cell death) if damage can’t be repaied.
 Apoptosis pathways

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