L312/Spring 2007Lecture 26Drummond April 26

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L312/Spring 2007 Lecture 26 Drummond April 26
Today Were done! Here are a few final
things to cover in class. This is the Ryan Smith
encouragement lecture. For praising the
analogies in-class there will be no exercise
today and everyone will get credit. Thank Ryan
and try to come up with your own analogy that
relates to a topic in the last two lectures (and
send it to me). Thurs., May 3 Final exam
1015 a.m.-1215 p.m., BH347 (note later time)
Exams are graded and recorded. Please pick
them up after class. Also, please pick up all
old drawing assignments. Anything not picked up
will be available outside my office (A303 JH, by
the library entrance) after class and until the
final exam. Review http//aimediaserver.com/stu
diodaily/videoplayer/?srcharvard/harvard.swfwidt
h640height520 full version
http//multimedia.mcb.harvard.edu Last study
guide will appear today (shortly) Modest review
(next page)
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Where do new tissue cells come from?
Which cells may become cancerous?
Take home
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More questions about tumorigenesis
Where is the benign/ Malignant crossover?
Where did all the Mutations come from? Tumors
are highly heterogeneous
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A possible APC-initiated progression
normal here one bad copy of APC (tumor
syndromes frequently recessive mutations)
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What does a cancer cell have that a normal cell
doesnt?

• They stop listening to their environment (often
  always on or off)
• dont respond to extracellular growth, mitosis,
  apoptosis, or survival
• They dont commit suicide in response to damage
  or abnormalities (e.g. a DSB)
• the apoptotic pathway is often disabled (p53 is a
  key checkpoint effector)
• They dont die of old age
• they maintain their telomeres by re-inducing
  telomerase
• They keep to a path of deviation from the
  original cellular mandate
• Most all tumors are genetically unstable (MIN or
  CIN)
• 1. can have epigenetic basis, e.g., DNA
  methylation normally silences
• They invade their neighbors
• They fail to make cadherins, or express the wrong
  ones, and export proteases
• Which key protein is the likely first target of
  proteases?
• They set up housekeeping in other tissues
• Cells can metastasize to other organs or tissues

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