Transcript Cell

BIOL 445 Cancer Biology
Spring 2012
Dr. Gidi Shemer
http://www.cancerquest.org/
Dr Andrejs Liepins/Science Photo Library
BIOL 445- Cancer Biology
Dr. Gidi Shemer
[email protected]
http://www.bio.unc.edu/Faculty/Shemer/
Office
Wilson Hall G41
Office hours
Tue 3:30- 5:00
Wed 10:00- 12:00
BIOL 445
This is NOT a med school course
445 = 202 + 205
- more depth
- a scientific/research approach
The course
- Introduction and overview
- What inputs a cell gets/oncogenes
- How cells react to inputs/tumor suppressor genes
Cell regulatory networks important in cancer cells
Hanahan and Weinberg, Cell 100:57-70 (2000)
BIOL 445
The course
- Introduction and overview
- What inputs a cell gets/oncogenes
- How cells react to inputs/tumor suppressor genes
- Cancer at the tissue and body levels
- Cancer therapy
BIOL 445
Textbook
The Biology of Cancer by Robert Weinberg
(also recommended: Natural Obsession by Natalie Angier)
What are you responsible for?
- Lectures
- Primary literature and assigned readings
- YOUR project- literature search and presentation
Grading
- Exams (28 X 3) = 84
- Project = 16
What Is Cancer?
Cells within a tissue are normally highly
organized and tightly regulated
e.g. intestine
e.g. skin
Cancer
Cells lose all controls
Can we fight cancer?
2007 Estimated US Cancer Deaths*
Lung & bronchus
31%
Men
289,550
Women
270,100
26%
Lung & bronchus
15%
Breast
Colon & rectum
Prostate
9%
Colon & rectum
9%
10%
Pancreas
6%
6%
Pancreas
Leukemia
4%
6%
Ovary
Liver & intrahepatic
bile duct
4%
4%
Leukemia
3%
Esophagus
4%
Non-Hodgkin
lymphoma
Urinary bladder
3%
3%
Uterine corpus
Non-Hodgkin
lymphoma
3%
2%
Brain/ONS
2%
Kidney
3%
Liver & intrahepatic
bile duct
All other sites
24%
ONS=Other nervous system.
Source: American Cancer Society, 2007.
23%
All other sites
This Lecture
- Properties of cancer cells
- Tumor progression
- Molecular basis of cancer
- What causes cancer?
Cancer: an aberration of normal development
Cancer cells exhibit behaviors found in normal
cells during development & differentiation
However, cancer cells behave independently
and do not “obey” controls
Properties of cancer cells
Most normal cells have a limited
potential to divide
senescent cells
Normal stem cells can divide
indefinitely, but under tight control
Differentiated cells
Self-renewing
stem cell
Cancer cells are "immortalized”,
just like stem cells, but w/o control
Differentiated cells
Self-renewing
stem cell
Cancer cell
Cancer cells do not differentiate
tumor
Normal cells may undergo
apoptosis
as part of a
developmental program
when cells become
“dangerous” (e.g. DNA
damage)
Cancer cells escape apoptosis
blue cells =
breast cancer cells
yellow cells =
apoptotic cells
Dave McCarthy and Annie Cavanagh
Cancer cells are invasive
normal
tissue
invasive
tumor
Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008)
Normal cells can be invasive at the
right time and place
Major Properties of Cancer Cells
- Cancer cells are "immortalized”
- Cancer cells do not form differentiated tissues
- Cancer cells escape apoptosis
- Cancer cells are invasive
Cancer: an Aberration of Normal Development
Cancer cells exhibit behaviors found in normal
cells during development & differentiation
However, cancer cells behave independently
and do not “obey” different controls
This Lecture
- Properties of cancer cells
- Tumor progression
- Molecular genetics of cancer
- What causes cancer?
Types of Cancers
Epithelial cells
Connective tissue
Muscle tissue
Epithelial cells: carcinomas
80-90%
Connective tissues: sarcomas 1%
Blood and lymphatic systems: leukemias, lymphomas
Neuronal system: neuroblastoma, retinoblastoma, etc.
Naming Cancers
Prefix
Meaning
adeno-
gland
chondro-
cartilage
erythro-
red blood cell
hemangio-
blood vessels
hepato-
liver
lipo-
fat
lympho-
lymphocyte
melano-
pigment cell
myelo-
bone marrow
myo-
muscle
osteo-
bone
Cancer develops through gradual changes
in cell morphology and properties
Tumor = abnormal growth of solid tissue
Cancer develops through gradual changes
in cell morphology and properties
Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008)
Cellular changes required for metastasis
Figure 20-44 Molecular Biology of the Cell (© Garland Science 2008)
This Lecture
- Properties of cancer cells
- Tumor progression
- Molecular genetics of cancer
- What causes cancer?
Cancer develops through gradual changes
in cell morphology and properties
Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008)
Cancer cells accumulate mutations
One mutation is not enough !!
A process of natural selection
Cancer cells accumulate
chromosomal abnormalities
Figure 20-13 Molecular Biology of the Cell (© Garland Science 2008)
What types of genes are mutated in cancers?
Two broad categories
Oncogenes
Gain of function mutations
Tumor suppressor genes
Loss of function mutations
Oncogenes
proto-oncogene
oncogene
A proto-oncogene: a normal cellular gene that
can become an oncogene, upon DNA damage
Cancerous mutations in proto-oncogenes
are dominant
dominant
recessive
e.g. the transcription factor- myc
Figure 20-27 Molecular Biology of the Cell (© Garland Science 2008)
Cancerous mutations in TSGs are recessive
dominant
recessive
Figure 20-27 Molecular Biology of the Cell (© Garland Science 2008)
Example
p53: the master guardian
Mutations in p53 can be found in half of all tumors
Figure 9.8 The Biology of Cancer (© Garland Science 2007)
Losing both copies of p53:
- No cell cycle arrest (over-proliferation)
- Angiogenesis
- No apoptosis
- No DNA repair (more mutations)
This Lecture
- Properties of cancer cells
- Tumor progression
- Molecular genetics of cancer
- What causes cancer?
What Causes Cancer?
Cancer : Accumulation of Mutations
- Random mutations (mistakes in the assembly line)
- Inherited mutations (pre-disposition)
- Viral infections
- Environmental factors (chemical; physical)
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
A sad British chimney sweep
Result: significantly lower rates of skin cancer
amongst Danish chimney sweeps, compared with
British, even a century later
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
Yamagiwa
Figure 2.21b The Biology of Cancer (© Garland Science 2007)
Carcinogens = agents that contribute to
the formation of a tumor
Figure 20-20b Molecular Biology of the Cell (© Garland Science 2008)
Summary
- Cancer cells exhibit behaviors found in normal
cells, but cancer cells are not under control
tumor
- Cancer develops through gradual
changes in cell properties
- Oncogenes and tumor-suppressor
genes are the molecules behind cancer
- Various factors lead to accumulation of
DNA damage and eventually to cancer