Cancer and the Cell Cycle

Chapter 2

The price we pay for being multicellular

Cancer is a complication of being a multiple-cell organism.

What causes cancer?

Cancer cells are abnormal cells that arise from the body’s normal tissue through mutations.

Mutated genes that cause cancer are called oncogenes.

It is thought that several mutations need to occur to give rise to cancer

Cells that are old or not functioning properly normally self destruct and are replaced by new cells.

However, cancerous cells do not self destruct and continue to divide rapidly producing millions of new cancerous cells.

Cancer Causing Agents

Ionizing radiation Chemicals in the envionment Virus infection http://

www.nih.gov/news/pr/jan2005/niehs-31.htm

Hereditary predisposition – Some families are more susceptible to getting certain cancers. Remember you can’t inherit cancer its just that you maybe more susceptible to getting it.

Central Points

Cancer involves uncontrolled cell division Mutations in certain types of genes such as

proto-onco genes and tumor supressor genes may lead to cancer. When genes are mutated and become cancer causing they are known as oncogenes.

Cancer is a disease that involves problems in the control of the cell cycle.

Breast, colon, and lung cancer are common types of cancer.

Benign or malignant? Benign tumours do not spread from their site of origin,

but can crowd out (squash) surrounding cells.

Malignant tumours can spread from the original site and cause secondary tumors. This is called metastasis. They interfere with neighbouring cells and can block blood vessels, the gut, glands, lungs etc.

Why are secondary tumours so bad?

Both types of tumour can tire the body out as they both need a huge amount of nutrients to sustain the rapid growth and division of the cells.

Cancer cells are abnormal cells that arise from the body’s normal tissue.

Environmental causes of cancer are being studied. Lawsuits have addressed smoking as a cause of cancer for example.

Central Points

Are malignant tumors monoclonal in origin? That is derived from a single ancestral cell that underwent conversion from a normal cell to a cancerous state? Or are malignant tumors polyoclonal in origin that is many individual cells become cancerous and the resulting tumor represents the descendents of these original cells.

Monoclonal or polyclonal

Cancer Cells

Animation: How Cells Reproduce

Cancer video

HHMI video

How Is Genetics Involved?

Two classes of genes: Oncogenes and tumor suppressor genes

Proto-oncogenes: control cell division

Tumor suppressor genes turn off cell division

Mutated alleles, oncogenes, and tumor suppressor genes cause cells to divide uncontrollably

Mutations in Tumor Suppressor Genes

1st mutation (susceptible carrier)

Active oncogene

No brakes!

Active oncogene

Normal genes (regulate cell growth)

Tumor suppressor genes

2nd mutation or loss (leads to cancer)

Tumor suppressor genes

No brakes!

Cancer-Causing Mutations

Exposure to environmental agents, virus, or lifestyle changes may cause a mutation

Certain virus infections can transform the cell

Human papillomavirus (HPV): Viral proteins interact with cell proteins, cause cervical cancer

Mistakes in DNA replication also cause mutations

4Cell

division

Mitosis

3DNA

repair

G21

Cell grows,

doubles in size

G1

S

2Chromosome

duplication

G2/M checkpoint

G1/S checkpoint

Regulation of Cell Cycle

G1/S checkpoint

G2/M checkpoint

Tumor suppressor genes and proto-oncogenes control these checkpoints• Tumor suppressor genes turn off or decrease rate

of cell division • Proto-oncogenes turn on or increase rate

Signal Transduction

In normal cells, signals from outside cell can• Activate tumor suppressor genes (turning off cell

division) or• Activate proto-oncogenes (turning  on  cell

division)

Signals can be proteins, hormones, or nerve signals

May include steroids, pollutants, and other molecules

Process of Signal Transduction

Signal binds to a receptor in plasma membrane

Binding sets off series of interactions inside cell

Signal molecule may remain outside cell

Binding of signal changes shape of receptor and allows it to transmit signal to other proteins

May alter gene expression

Outside cell

Receptor

Plasma membrane

Cytoplasm

Nucleus

Changes in gene expression

Signal molecule

Signal–receptor binding

Cellular response

Protein molecules

Ras Signaling This is a detailed view of Ras interactions in pathways leading to:• cell proliferation• cell survival• differentiation• cell cycle control• cell motility• tumorigenesis

Proto-Oncogene RAS (1)

Produces RAS protein that:• Attaches to inside of plasma membrane• Is part of a pathway that turns on cell division• Is signaled by growth factors from outside the cell• Changes shape and switches on when activated• Transfers signal to another protein in pathway• Changes shape again after signal transmitted,

switches off (inactive)

Proto-Oncogene RAS (2)

RAS mutations in many types of cancer, including colon, lung, pancreatic, and stomach cancer

Mutant RAS stuck “on” and produces uncontrolled cell division

Cancer Genes on other Chromosomes

Environmental Factors and Populations

Determine types of cancer populations may develop

Many forms of cancer related to: • Physical surroundings• Personal behavior• Or both

At least 50% of all cancer can be attributed to some type of environmental factor

Spotlight on Ethics: HeLa Cell Line (1)

In 1951, cervical cells removed from Henrietta Lacks during biopsy

She died from cervical cancer

Cells maintained in vitro (in the lab) and used for worldwide scientific study

HeLa cells immortal because they can divide an

unlimited number of times in a laboratory

Spotlight on Ethics: HeLa Cell Line (2)

Originally grown without Lacks’ knowledge or permission and later sold to medical schools

Have been used for commercial products: HPV vaccine