The Loss of the Cell Cycle Control in Cancer

Part 3: Page S90 Lab Manual

Loss of Cell Cycle Control in CancerPrelab Questions for Part 3

• How are normal cells and cancer cells different from each other?

• What are the main causes of cancer?

• What goes wrong during the cell cycle in cancer cells?

• What makes some genes responsible for an increased risk of certain cancers?

What are the roles of tumor-suppressors genes and onco-genes?

What seems to be genetically wrong in families with a history of cancer?

Stating a Hypothesis

Do you think that the chromosomes might be different between normal and cancer cells?

Tumor-suppressor Genes:One of the most important molecules relating to

cancer is called p53. It has been called the guardian of the genome.

Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don't work properly, cells can grow out of control, which can lead to cancer.

1) Why is p53 important in controlling the cell cycle?

An important difference between oncogenes and tumor suppressor genes is that oncogenes result from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer when they are inactivated (turned off).

Inherited mutations of tumor suppressor genes

Inherited abnormalities of tumor suppressor genes have been found in some family cancer syndromes. They cause certain types of cancer to run in families. For example, a defective APC gene causes familial adenomatous polyposis (FAP), a condition in which people develop hundreds or even thousands of colon polyps. Often, at least one of the polyps becomes cancer, leading to colon cancer.

Acquired mutations of tumor suppressor genesAbnormalities of the p53 protein have been

found in more than half of human cancers. Acquired mutations of this gene appear in a wide range of cancers, including lung, colorectal, and breast cancer.

The p53 protein is involved in the pathway to apoptosis. This pathway is turned on when a cell has DNA damage that can't be repaired. If the gene for p53 is not working properly, cells with damaged DNA continue to grow and divide. Over time this can lead to cancer.

Acquired changes in many other tumor suppressor genes also contribute to the development of sporadic (not inherited) cancers.

Many of the genetic alterations found in cancer cells are microscopically visible when chromosomes condense during mitosis, and can thus be registered as numerical or structural cytogenetic abnormalities that can be studied – including karyotypes.

Chronic myelogenous leukemia, showing the typical 9;22 translocation

Chronic myelogenous leukemia, showing the typical 9;22 translocation

The Philadelphia chromosome (Ph) is

produced by a translocation between

the long arms of chromosomes 9 and

22.

Non-small-cell carcinoma of the lung, showing abnormalities of both number and structure.

HeLa Karyotype

Burkitt’s LymphomaTranslocation: misplacement of chromosome 8

Dermatofibrosarcoma: Chromosomes

DermatofibrosarcomaTwo distinct cytogenetic features,

supernumerary rings and translocations

You have received a set of chromosomes to build your own karyotype. Follow all the instructions given on

the handout!For each of the following cases, look at pictures of the

chromosomes (karyotype) from normal human cells. Compare them to pictures of the chromosomes from cancer cells. For each case, count the number of chromosomes in each type of cell, and discuss their appearance. Then answer the following questions.

• Do your observations support your hypothesis?• If not, what type of information might you need to

know in order to understand your observations?• If yes, what type of information can you find that

would validate your conclusions?Abnormal Karyotypes

Case 1: HeLa cellsCase 2: Philadelphia ChromosomesFor each of the following cases, look at pictures of the chromosomes (karyotype) from normal human cells. Compare them to pictures of the chromosomes from cancer cells. For each case, count the number of chromosomes in each type of cell, and discuss their appearance. Then answer the questions in your lab textbook for this section.

Anaplastic large-cell lymphoma # 6Burkitt’s lymphoma # 7Chronic myelogenous leukemia # 2Dermatofibrosarcoma protuberans # 10Ewing’s sarcoma # 11Follicular lymphoma # 8Hela # 5Mantle cell lymphoma # 4Synovial sarcoma # 9

Karyotypes of Cancerous Cells

Analysis of your cancer research

1)Which tissues are affected?2)Symptoms3)Treatments4)Prognosis: forecasting of the

probable course and outcome of a disease, especially of the chances of recovery (curable, treatable, terminal for how long).