Cell signaling and cancer

From Inside Cancer Wiki

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Cell Signaling and Cancer

Lesson Overview

This lesson is designed to introduce students to the principles of cell signaling and its relationship to cancer. Using the Inside Cancer web site students observe the sequence of events that occur as a result of the arrival of a chemical messenger at the external surface of the cell. The animations dramatize the events that lead to the cell’s response to the messenger. After examining the fundamentals of cell signaling pathways, students move on to examine the ramifications of mutations that lead to abnormal functioning of these pathways. In this context, the focus will be on the development of cancer.

Goals and Objectives Students will be able to:

• recognize that cell growth and division occurs in response to specific chemical signals.

• list and describe the sequence of events that occurs in a signaling pathway from the release of the chemical messenger to the initiation of the cellular response.

• characterize and distinguish key proteins involved signaling pathways involved in cell growth and proliferation.

• explain how mutations to some of these proteins can lead to cancer.

• identify specific cancers that result from mutations to signal pathway proteins.

• Explain how targeted therapies can be used to treat cancers that result from aberrations to signaling pathways involved in cell growth.

Common Misconceptions

• Students often think that cells just “know” when to divide.

• Students presume that mitosis comprises the bulk of the cell cycle.

• Students are unaware of the controls present that regulate cell growth and division.

• Students perceive proteins as working independently.

• Students often think proteins are rigid and don’t realize that changes in protein shape are critical to their activity.

The Lesson

Preparation Before class: (materials, handouts etc.) Photocopy the Media:Cell_Signaling_and_Cancer.doc for students so they can write their answer directly in the document. However, because the links to the necessary online sites are embedded in the text, it may also be preferable to have students access an electronic version as well.

During class Students will be working through the document and the web page during class, allowing the teacher to circulate, addressing any questions or conceptual difficulties the students may be having. It is also suggested that at various intervals during the class session time-out is taken from individual work to have a brief class discussion on what has been discovered. This provides more opportunity for student questions and more in-depth examination of the topic. (See resources section for additional sources of information on cell signaling). Class time should also be allocated for the “talks.” Time required

Cell Signaling Mechanisms – 1 class session. If students do not complete the activity during class time, it can be finished at home, with the answers to the questions brought to the next class session for review.

Cell Signaling and Cancer - 1 class session. If students do not complete the activity during class time, it can be finished at home, with students bringing their notes to the next class session for discussion. Final Assignment – Students should be provided adequate time to research and prepare their talk and poster. It is suggested that 1 class session be devoted to student research so any questions they may have can be addressed.

Student Handouts for the Lesson Plan

Media:Cell_Signaling_and_Cancer.doc

Alternative Assessments

Recommendations for Evaluation:

• Teachers may choose to collect and evaluate the answers generated by students to questions asked throughout the activity. The answers can be found here: Media:Cell_Signaling_and_Cancer_answers_to_questions.doc

• A quiz on the nature of signaling pathways could be used to assess student understanding of biology of familial breast cancer.

• Assessment of the talk and poster should be done. It is suggested that a rubric for assessment be passed out ahead of time to help students recognize the standards that must be met when giving an oral presentation.

Suggestions for Extended Learning

This lesson can be augmented by investigating specific signaling pathways. In this lesson a generalized version of the pathway is studied, however studying specific types of cell receptors and the pathway mechanisms they are involved with can be done. An investigation into Tyrosine Kinase Receptors, G- Protein Linked Receptors, and Gated Ion Channels will lead student to discover the extent to which signaling pathways are used by cells to carry out myriad cell functions.

Glossary

Cell Receptor – A protein that binds with a specific chemical signal. The receptor may be an integral membrane protein that extends from the external surface of the cell or found in the cytoplasm

Chemical Signal (Messenger) – A chemical compound synthesized by cells and released into the environment that binds to specific receptors found on or in a target cell. Commonly known as a ligand.

Chronic Myeloid Leukemia – A form of blood cancer that results from the excessive activity of a protein kinase involved in a signaling pathway that leads to cell growth and proliferation. The kinase causing this cancer is produced from the fusion of two genes, BCR and abl. The fusion occurs as a result of a reciprocal chromosomal translocation.

Estrogen - A hormone of the female reproductive system. Certain types of breast cancer require this hormone in order to grow.

Fos - A protein, found in the nucleus that is activated during a cell signaling pathway. It operated in conjunction with Jun and serves to “turn on” the expression of specific genes needed in the cell response to the chemical signal received by the cell.

Gleevac – A drug that binds to the active site of the BCR-abl kinase. This binding blocks the ability of the enzyme from activating other proteins in the signaling pathway where it works. This restricts cell growth and division and the cell eventually dies. Gleevac is a targeted drug therapy used to treat Chronic Myeloid Leukemia.

Growth Factor - A protein that acts as a chemical messenger to promote cell growth and division.

Growth Factor Receptor – Protein receptor found on the external surface of cells that specifically binds a growth factor to initiate a signal pathway that leads to cell growth and proliferation.

Her-2 – A specific example of a growth factor receptor found on the cells of breast tissue. Certain types of breast cancer are characterized by cells that have excessive expression of the Her-2 receptor.

Herceptin – An antibody that is manufactured to compete with growth factors that bind to the Her-2 receptors found on cells from breast tissue. The binding of Herceptin to Her-2 prevents the binding of the growth factor, thus inhibiting growth of the cell.

Hormone - A chemical substance produced in the body that controls and regulates the activity of certain cells or organs.

Jun - A protein, found in the nucleus that is activated during a cell signaling pathway. It operated in conjunction with Fos and serves to “turn on” the expression of specific genes needed in the cell response to the chemical signal received by the cell.

Kinase - An enzyme that phosphorylates its substrate. The source of the phosphate is ATP.

Ras – A key protein found in signaling pathways. Ras is found in the cytoplasm and activated early in the pathway. It, in turn, activates a protein known as Raf, to transmit the signal through the cell. A number of cancers are characterized by mutations that leave Ras in the “on” position so that it is constantly activating protein of the signal pathway. This results in uncontrollable growth of the cells.

Transcription – The process of synthesizing an RNA molecule from a DNA template.

Translation - The process of synthesizing a protein from the instructions carried on an mRNA molecule.

Signal Transduction – Another name for “cell signaling” or “signaling pathway.”

Teacher Answer Key [ Cell Signaling and Cancer - teacher pages]