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Cell Signaling and Cancer

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					Cell Signaling and Cancer

1. Introduction

Cell growth and division is a function that characterizes all living organisms. Looking at your
own body you can identify numerous examples of cell division occurring at this very moment:

       Cell division of skin cells to replace those that have died and sloughed off.
       Cell division of skin cells to fill in a wound
       Cell division of stomach cells to replace those that have been damaged due to exposure
        to the hydrochloric acid released into the stomach

These are just a few examples of the cell cycle in action. The cell cycle is a sequence of events
that involves growth and division. When studying human cells growing in culture, the cell cycle
takes about 24 hrs1. Observing the events under a microscope, the processes of nuclear and cell
division are quite striking. However, you would have to be sitting at the lab bench for 23 hrs
before you saw anything actually happen! So, what is happening in the interim between actual
cell divisions? The key event is growth, with most cells doubling in size between divisions1.
While cells carry out normal metabolic activity during the time between divisions, recognizing
that growth must be accompanied by cell division, cells also duplicate their genetic material
during this time. When the cell reaches a certain size, it divides.

How does a cell “know” when it is time to divide? What controls these events to ensure that
the division occurs properly and correctly? These are critical questions to scientists who study
the cell cycle because not only do their answers provide insight into normal cell function, their
answers help us better understand diseases that arise when the process goes awry.
2. Cell Signaling Mechanisms

Simply put, cells respond to specific chemicals that signal them to divide. While there are a
countless pathways utilized by cells, they all display the same fundamental characteristics. All
“signal pathways” involve a chemical messenger, a protein receptor, and a cellular response. To
see how these components of the signaling pathway work together, watch the following series
of animations at the Inside Cancer web site.

       Go to Inside Cancer: www.insidecancer.org
       Choose ”Pathways to Cancer” from the menu across the top.
       Begin with the ”Overview” by selecting that tab from the menu on the left side of the
        screen
       Read through the first two slides, then click “At the cell surface” from the menu bar on
        the left side of the screen
       Select ”Video with narration” from the viewing options menu.
       As you watch the animation and listen to the narrative, answer the questions below to
        ensure your understanding is complete and accurate.


At the cell surface: Questions to Answer

    1. Provide two examples of chemical signals that might start the signaling pathway.


    2. List 3 things that happen when the signal interacts with its cell surface receptor?




    3. The cell is exposed to many different chemical signals at any given time. What ensures
       that the proper signal binds to initiate the desired cell response?




       When the animation is complete click “Beneath the cell membrane” to continue
        studying the signal pathway.
Beneath the cell membrane: Questions to Answer

   1. Describe how the part of the receptor on the inside of the cell responds to the binding
      of chemical signal.




   2. Once the internal portion of the receptor has been activated, how is the signal relayed
      through the cell?




      When the animation is complete click “A bevy of interactions” to continue studying the
       signal pathway.


A bevy of interactions: Questions to Answer


   1. Place the following labels on the diagram below

              Protein Receptor
              Ras
              Raf
    2. Keeping in mind that you are looking at cell signaling mechanisms to understand how
       cells control growth and division, hypothesize why a mutation in the gene for the Ras
       protein might lead to cancer.

           If you are unsure about how to answer this question navigate to the “Hallmarks of
            Cancer” section of the Inside Cancer website.

                 Click on “Hallmarks of Cancer” from the menu at the top of the page
                 Click on the tab labeled “Growing uncontrollably” from the menu on the
                  left side of the page.
                 Work through the 4 slides presented.
                 After reading the text and listening to the interviews, go back and try to
                  answer the question.




       When the animation is complete click “To the nucleus” to continue studying the signal
        pathway.


To the nucleus: Questions to Answer

    1. What is a kinase? What role does it play in the cell signaling pathway?



    2. Since all cell signaling pathways end with a cellular response, explain why it is important
       that the cellular proteins that have been activated by the binding of the signal make
       their way to the nucleus. Hint: What role does the nucleus play in cell function? What
       processes take place there that might be involved in a cellular response to a chemical
       signal?



.
      When the animation is complete click “Inside the nucleus” to continue studying the
       signal pathway.



Inside the nucleus: Questions to Answer

   1. After viewing the animation, edit your response to the question in “To the nucleus.”
      Did you identify the correct process occurring in the nucleus that begins the cell’s
      response to the signal?


   2. What is the role of Fos and Jun?




      When the animation is complete click “Making the protein” and “Completing the
       protein” to complete your study of how a signal pathway works.



Making the Protein and Completing the Protein: Questions to Answer

   1. Distinguish between the processes of transcription and translation.




   2. What is the function of the Golgi apparatus?




   3. Assume the protein being synthesized in this animation is a growth factor. What is the
      fate of this protein? In other words, once it is packaged by the Golgi, what will it do and
      how will it do it?
3. Cell Signaling and Cancer

Cancer is a disease that is characterized by uncontrollable cell growth. If you did not visit the
“Hallmarks of Cancer” section of Inside Cancer (www.insidecancer.org) earlier, go there now to
get more information on the features of this disease.

             Go to www.insidecancer.org
             Click on “Hallmarks of Cancer” from the menu at the top of the page
             Click on the tab labeled “Growing uncontrollably” from the menu on the left
              side of the page.
             Work through the 4 slides presented.

As you learned from the interviews, cancer cells have the ability to grow in the absence of
growth stimulating signals. This ability often results from mutations that affect the signaling
pathways used by the cell. To get some background on how mutations to cell signaling
mechanisms can lead to cancer return to Inside Cancer (www.insidecancer.org) and follow the
instructions below. Take notes on what you read and see for use later in the exercise.

1.
               Go to www.insidecancer.org
               Click on “Causes and Prevention” from the menu at the top of the page
               Click on the tab labeled “Smoking” from the menu on the left side of the page.
               Select K-ras from the picture box by clicking on the arrow.
               Read through the slides. The information provided should be familiar to you
                based on the work you did on the “Pathways to Cancer” section earlier.

2. Now look at a second example of a mutation that affects a cell signaling pathway, with the
end result being cancer.

             Go to www.insidecancer.org
             Click on “Diagnosis and Treatment” from the menu at the top of the page
             Click on the tab labeled “Blocking Receptors” from the menu on the left side of
              the page.
             Read through the slides and listen to the interviews. Again take notes on
              what is being presented for use later on.
             Note: The first example shown in this part of the web site deals with estrogen.
              Estrogen is a female reproductive hormone and like many hormones serves as a
              chemical signal. The key difference in the action of estrogen, compared to the
              chemical signals you have looked at so far, is that estrogen binds to its receptor
              inside the cell. Once it diffuses into the cell and binds to the receptor the
              signaling pathway is initiated.
3. For a third example of how problems in cell signaling can lead to cancer, return to the
“Pathways to Cancer” section you worked through in part 2 of the lesson.

             Go to www.insidecancer.org
             Click on “Pathways to Cancer” from the menu at the top of the page
             Select “At the cell surface” from the tab on the left.
             Start the animation (it won’t hurt to hear the information again) and wait until
              the menu box at the end comes up. Click the “enter” button to learn more
              about the molecules shown in the animation.
             Run the arrow over the molecules until you find the “Platelet Derived Growth
              Factor Receptor.” Read the associated text found below the image to learn
              about how mutations to this protein can lead to cancer. Be sure to note as
              many details as possible on how cancer can develop and on specific examples
              related to PDGF receptors that have been shown to cause cancer.
             Now select ”Beneath the Membrane.” Watch the animation again and then
              click “enter” to learn more about the molecules. Find the Ras molecule and
              then read the associated text. Note: there is a lot of detail provided. Focus,
              your attention on the role Ras plays in the signal pathway that leads to cell
              growth and on what happens if there is a mutation to the Ras gene. The
              information here should reinforce what you learned earlier about K-ras.

4. The final example of how mutations to genes coding for proteins involved in cell signaling can
result in cancer can be found back in the “Diagnostics and Treatment” section of Inside Cancer.

             Go to www.insidecancer.org
             Click on “Diagnosis and Treatment” from the menu at the top of the page
             Click on the tab labeled “Targeted Activators” from the menu on the left side of
              the page.
             Select “Gleevac and Chronic Myeloid Leukemia” by clicking on the arrow.
             Read through the slides 1 and 2 listening to the interview and working through
              the animation provided on slide 2. Again take notes on what is being
              presented for later use.
4. Final Assignment

You have been invited to attend an upcoming Cold Spring Harbor meeting on cell signaling
pathways. Specifically, you have been asked to speak on the role cell signaling plays in cancer.
To prepare for your talk you will research one specific example of a problem in a signaling
pathway that has been shown to lead to cancer. Your talk must include the following:

       Background information on the general way cell signaling pathways work.
       An explanation of the role the protein you have selected plays in the signaling pathway
        when it functions normally.
       An explanation of how and/or why mutations in your protein lead to cancer.
       Identification of examples of known cancers caused by a mutation in the protein you
        have selected.
       A discussion of any current therapies in use or being developed to treat the cancer that
        results from the mutation to your protein.

To accompany your talk you must prepare a poster. The poster should illustrate the ideas you
are presenting in the talk. Your poster should have a descriptive title that makes it clear to the
reader the topic of the poster. In addition, clear, concise captions should be provided to explain
the pictures presented. Finally, the pictures and captions should be large enough to be viewed
from a distance of 3 feet.

 You do not need to reference your poster during the talk (you may chose to use PowerPoint
instead), but the poster will be on display for future reference.


The information you have obtain for Inside Cancer is an excellent place to start your research
for you talk. The following list identifies other internet sites that may be useful.

    1. The National Cancer Institute – www.cancer.gov
    2. PubMed Central Homepage - www.pubmedcentral.nih.gov/
            PubMed Central (PMC) is a free digital archive of biomedical and life sciences
              journal literature
            You can begin your search here by simply typing your topic into the search bar
            A list of articles will come up. Read the titles to see if any seem appropriate.
              For those that look promising, click on “abstract” to read a synopsis of the
              article.




Bibliography
1. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.section.2433

				
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