biol 445 cancer biology mark peifer and bob duronio spring 2015
TRANSCRIPT
BIOL 445 Cancer Biology
Mark Peifer and Bob Duronio
Spring 2015
BIOL 445
In Bio 445 we combine the approaches of Bio 202 + Bio 205with the current scientific literatureto study the family of diseases known as cancer
You may not believe it but by the end of the semesterThis will make sense!
Hanahan and Weinberg, Cell 100:57-70 (2000)
Virtually everything you’ll need is found at:
http://www.bio.unc.edu/Courses/2015Spring/Biol445/
It’s a REALLY good idea to look through this carefully THIS WEEK
AND
Check back frequently for updates or changes
We will also us the course Sakai site for online quizzes, Blogs, and as a place for a discussion forum
BIOL 445Textbooks-The Biology of Cancer by Robert Weinberg 2nd Edition
Grading- Exams (20% X 2 midterms + 25% final) = 75- Presentations = 15- Classroom discussion, online and in-class evaluations = 10
What are you responsible for?- Lectures (attendance AND participation)- Papers and assigned textbook reading(on website)-Your project- literature search and presentation
Your Project
- Choose a topic
- Read the posted review paper
- Do a thorough literature research, including primary data on the gene and the disease
- Make a poster and present it to your peers
- The final exam will cover ALL posters
Cancer: a family of diseases
caused by our own cells gone wrong
Cancer is number 2
and rising relative to heart disease!
CDC
ONS=Other nervous system.Source: American Cancer Society, 2009.
But as we’ll see, Cancer is not one disease, its many
Lifetime Probability of Developing Cancer, By Site, Men, US, 2007-2009
SiteRisk
All sites 1 in 2
Prostate 1 in 6
Lung and bronchus 1 in 13
Colon and rectum 1 in 19
Urinary bladder 1 in 26
Non-Hodgkin lymphoma 1 in 43
Melanoma 1 in 40
Kidney 1 in 49
Leukemia 1 in 63
Oral Cavity 1 in 67
Stomach 1 in 92
Source: ACS http://www.cancer.org/Cancer/CancerBasics/lifetime-probability-of-developing-or-dying-from-cancer
Lifetime Probability of Developing Cancer, By Site, Women, US, 2007-2009
Site Risk
Source: ACS http://www.cancer.org/Cancer/CancerBasics/lifetime-probability-of-developing-or-dying-from-cancer
All sites 1 in 3
Breast 1 in 8
Lung & bronchus 1 in 16
Colon & rectum 1 in 21
Uterine corpus 1 in 38
Non-Hodgkin lymphoma 1 in 52
Melanoma 1 in 63
Pancreas 1 in 69
Ovary 1 in 72
Kidney 1 in 83
Urinary bladder 1 in 87
We are making progress, however!!
March 28.2012
Cancer is NOT an infectious disease
Cancer is NOT an infectious diseaseInstead it illustrates the challenge of understanding how genetics and the
environment combine to cause disease
To understand what goes WRONG,we need to understand
how things normally go right
Cells within a tissue are normally highly organized and tightly regulated
e.g. intestine e.g. skin
Cancer: an aberration of normal development
Cancer cells exhibit behaviors found in normal cells during development,
differentiation, and homeostasis
Cancer: an aberration of normal development
Cancer cells exhibit behaviors found in normal cells during development,
differentiation, and homeostasis
However, cancer cells put together suitesOf cell behaviors in problematic ways
And do so out of normal regulatory controls
All cancers have a genetic basis--they are diseases of our own cells gone wrong
Sometimes inherited mutations play a role.e.g., Familial adenomatous polyposis (FAP) =inherited predisposition to colon cancer
However, most cases result from the Slow accumulation of
Somatic mutations
Cancer results from a
series of mutations, each further
altering the cell
Lodish et al.Fig. 24-6
The last two years has seen a revolution in our knowledge of the full array of mutations in many tumor types
Most normal cells have a limited potential to divide
senescent cells
Properties of Cancer Cells
Normal stem cells can divide indefinitely, but under tight control
Self-renewing stem cell
Differentiated cells
Cancer cells are "immortalized”,just like stem cells, but w/o control
Properties of Cancer Cells
Self-renewing stem cell
Differentiated cells
Cancer cell
Most Normal cells differentiate
But stem cells do NOT
differentiate
Like normal stem cells Cancer cells do not differentiate
tumor
Figure 20-29 Molecular Biology of the Cell (© Garland Science 2008)
Most normal cells stop proliferating under contact inhibition
in vitroin vivo
Figure 20-29 Molecular Biology of the Cell (© Garland Science 2008)
Cancer cells are not under contact inhibition
However cells of early embryosalso lack contact inhibition, but then gain it at themid-blastula transition
Normal
“Transformed”
Cancer cells have alterations incell adhesion
and the cytoskeleton
Look out-Here I Come!
Cell from:www.basic.northwestern.edu/ g-buehler/micropl.jpg
These changes in cell shape and behaviorare shared by many migrating cells,including those that migrate into wound sites
Late stage cancer cells are invasive
Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008)
normal tissue
invasive tumor
Normal cells can be invasive at the right time and place
Seward Hung
Normal cells that are starved for O2 Induce Angiogenesis
Consequences 1. Nutrients and oxygen are supplied to the tissue
Can’t breath!Send Blood vessels
Cancer Cells also Induce Angiogenesis
Consequences 1. Nutrients and oxygen are supplied to the tumor2. New blood vessels provide as easy way out
Some properties of Cancer Cellsinvolve evading normal behaviors that
limit growth and prevent damage
Normal cells may undergo apoptosis
as part of a developmental program
when cells become “dangerous” (e.g. DNA
damage)
Properties of Cancer Cells
Cancer cells escape apoptosis
blue cells = breast cancer cells
yellow cells = apoptotic cells
Dave McCarthy and Annie Cavanagh
Cancer: an aberration of normal development
Cancer cells exhibit behaviors found in normal cells during development,
differentiation, and homeostasis
However, cancer cells put together suitesOf cell behaviors in problematic ways
And do so out of normal regulatory controls
- Cancer cells do not form differentiated tissues
- Cancer cells are not under contact inhibition
- Cancer cells are "immortalized”
- Cancer cells are invasive
Properties of Cancer Cells
- Cancer cells escape apoptosis
This Lecture- Properties of cancer cells
- Tumor progression
- What causes cancer?
- Accumulation of mutations
Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008)
Cancer develops through gradual changesin cell morphology and properties
Tumor Progression
Tumor = abnormal growth of solid tissue
benign- self contained
malignant- invasive
Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008)
Metastasis is a difficult and dangerous process both for the tumor cell and the host!
This is what you do NOT want
Cellular changes required for metastasis
Figure 20-44 Molecular Biology of the Cell (© Garland Science 2008)
This Lecture- Properties of cancer cells
- Tumor progression
- What causes cancer?
- Accumulation of mutations
What Causes Cancer?
- Random mutations (mistakes at the assembly line or induced by environment)
- Inherited mutations (pre-disposition)- Viral infections (cervical cancer and a few rare
types)
Cancer : Accumulation of Mutations
The first association between occupation and cancer
Percivall Pott found that chimney sweeps show substantially higher rates of skin cancer
British chimney sweeps didn’t do anything about it
Danish chimney sweeps : a daily bath after work
Result: significantly lower rates of skin cancer amongst Danish versus British chimney sweeps,
even a century later
A happy Danish chimney sweep
at work
with the family
Figure 2.21b The Biology of Cancer (© Garland Science 2007)
Yamagiwa
Yamagiwa took it one step further
Coal tar condensates induced skin carcinoma in rabbits
Chemicals can directly induce cancer
Cancer can be studied in the lab
Figure 20-20b Molecular Biology of the Cell (© Garland Science 2008)
Carcinogens = agents that contribute to the formation of a tumor
Can YOU see the trend in the data?
This Lecture- Properties of cancer cells
- Tumor progression
- What causes cancer?
- Accumulation of mutations
Cancer often starts with a single mutation
HoweverOne mutation is not enough !!
Heard of natural selection?
Figure 20-7 Molecular Biology of the Cell (© Garland Science 2008)
The fact that cancer is a multi-step process is reflected in correlation between age and incidence of cancers
Cancer cells also accumulate chromosomal abnormalities,especially late in the process
Figure 20-13 Molecular Biology of the Cell (© Garland Science 2008)