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					Cancer: Cell Division
Out of Control
What is Cancer?
 Control and coordination of cells is vital
 Loss of control results in chaos and
death
 Cells respond to signals to divide
 Cancer is the loss of this control
Development of Cancer
Growth regulators
   Some factors promote cell growth
    

   Some factors inhibit cell growth
    

   These are balanced to control cell division
Viral Cancer
   Rous Sarcoma virus




   DNA was sequenced
    
Kinases
   Common positive growth regulators
    

   Add phosphate to other proteins
   Regulate the activity of these proteins
Oncogenes
   Mutated forms of growth regulatory genes
    

   DNA mutations cause proto-oncogenes to
    become oncogenes

Negative Growth Regulators




   Provide internal safeguards
    


Retinoblastoma







Function of Rb
                                                                                 Protein production
                                                                                   needed for cell
                                                                                      division


                                                                                             Cytosol
              Cell
                                              Cell
            CANNOT
                                              CAN
             Divide
                                             Divide
                                                      Inactive Rb
                      Inactive                        protein
                      Regulatory
                      protein                                                             Nucleus
                                                               Released
                                                               activated
                                                               regulatory
Active Rb                                                      protein
                                   Activated
protein                            Protein kinase




                                                                            Target gene
Function of Rb
   Each cell has two of each chromosome
    

   One good gene can inhibit tumor growth
   Both Rb genes must be mutated
    
Positive and Negative Regulation
                  Two copies of tumor
                  suppressor gene

Negative
regulation
                                                                Both tumor suppressor
Cell
                                                                genes are inactivated
Division
Control
System
Positive
regulation

                  Result:                Result:                          Result:
 Two copies of                                      Mutated
                  No cell               Excessive                        Excessive
 proto-oncogene                                     proto-oncogene:
                  division               division                         division
                                                    Oncogene
Incidence of Cancer
Cancer is a Multi-step Process
   Progression to cancer is step-wise
   Several cellular safeguards have to fail
    

   Several mutations must occur
Progression
of Cancer

   Multi-hit
    theory
Cancer and Lifestyle
   Environmental factors
   Smoking related cancers
    

   Tobacco smoke
    
    
p53: Vital Tumor Suppressor

     Allows   DNA repair or causes cell death
   If moderate DNA damage
    
    

   If severe DNA damage
    

				
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