Cancer cells

1
Cancer cells

• Fig. 25.11

2
25.1 Control of gene expression

• Diploid cells are totipotent
• Contains all genes necessary to develop into an
  entire organisms
• Reproductive cloning
• Dolly the sheep- proved that animals can be
  cloned
• Accomplished by starving an enucleated cell prior
  to implanting a new nucleus- forces cell into G0
• Therapeutic cloning
• Produces various cell types rather than a whole
  organism
• Provides cells and tissues to treat diseases
• Allows us to gain information about
  differentiation

3
Control of gene expression contd.

• Two methods of therapeutic cloning
• Use of embryonic stem cells
• Similar method as reproductive cloning
• Cell is directed to become a specific cell or
  tissue type rather than a complete organism
• Ethical considerations- each cell could have
  potentially become an individual
• Use of adult stem cells
• Many tissues have stem cells-skin, bone marrow,
  umbilical cord cells
• Adult stem cells may not give rise to all cell
  types
• Research is currently underway to develop
  techniques to allow adult stem cells to give rise
  to all other cell types

4
Two types of cloning

• Fig. 25.1

5
Control of gene expression contd.

• Gene expression in bacteria
• Studied in bacteria because it is simpler than
  eukaryotes
• E. coli lac operon- all 3 enzymes for lactose
  metabolism are under the control of one promoter
• Promoter- short DNA sequence where RNA polymerase
  first attaches
• Three structural genes each code for an enzyme
  necessary for lactose metabolism
• Promoter and structural genes together are called
  an operon

6
Control of gene expression contd.

• Gene expression in bacteria contd.
• Repression of the lac operon in E. coli
• When lactose is absent in the environment, then
  enzymes for lactose metabolism are not necessary
• Regulatory gene outside of operon codes for a
  repressor protein
• Repressor protein binds to the promoter and
  prevents the structural genes from being
  transcribed
• Induction of the lac operon in E.coli
• When lactose is present it binds to repressor
  protein
• This frees the promoter site and RNA polymerase
  can bond
• Transcription of structural genes occurs

7
The lac operon

• Fig. 25.2

8
Control of gene expression contd.

• Gene expression in eukaryotes
• Housekeeping genes- control essential metabolic
  enzymes or structural components that are needed
  all the time
• Very little regulation
• Levels of gene control
• Unpacking of DNA
• Chromatin packing is used to keep genes turned
  off
• Heterochromatin-inactive genes located within
  darkly staining portions of chromatin ex. Barr
  body
• Euchromatin-loosely packed areas of active genes
• Euchromatin still needs processing before
  transcription occurs
• Chromatin remodeling complex pushes aside histone

9
X-inactivation in mammalian females

• Fig. 25.3

10
Control of gene expression contd.

• Levels of gene control in eukaryotes contd.
• Transcription
• Most important level of control
• Enhancers and promoters on DNA are involved
• Transcription factors and activators are proteins
  which regulate these sites
• mRNA processing
• Different patterns of exon splicing
• Translation
• Differences in the poly-A tails and/or guanine
  caps may determine how long a mRNA is available
  for translation
• Specific hormones may also effect longevity of
  mRNA

11
Control of gene expression contd.

• Levels of gene control in eukaryotes contd.
• Protein activity
• Some proteins must be activated after synthesis
• Feedback controls regulate the activity of many
  proteins

12
Levels of gene expression control in eukaryotic
cells

• Fig. 25.4

13
Control of gene expression contd.

• Transcription factors and activators
• Transcription factors- proteins which help RNA
  polymerase bind to a promoter
• Several transcription factors per gene form a
  transcription initiation complex
• Help in pulling DNA apart and in the release of
  RNA polymerase for transcription
• Transcription activators- proteins which speed up
  transcription
• Bind to an enhancer region on DNA
• Enhancer and promoter may be far apart-DNA must
  form a loop to bring them close together

14
Transcription factors and enhancers

• Fig. 25.5

15
Control of gene expression contd.

• Signaling between cells
• Cells are in constant communication
• Cell produces a signaling molecule that binds to
  a receptor on a target cell
• Initiates a signal transduction pathway- series
  of reactions that change the receiving cells
  behavior
• May result in stimulation of a transcription
  activator
• Transcription activator will then turn on a gene

16
Cell-signaling pathway

• Fig. 25.6

17
25.2 Cancer a failure of genetic control

• Characteristics of cancer cells
• Form tumors
• lose contact inhibition and pile on top of each
  other and grow in multiple layers
• Lack specialization
• nonspecialized and do not contribute to normal
  function of tissue continue to go through the
  cell cycle
• Abnormal nuclei
• large nuclei with abnormal chromosome numbers
• Spread to new locations
• release a growth factor that promotes blood
  vessel growth, and enzymes that break down the
  basement membrane cancer cells are motile and
  can travel in blood and lymph

18
Development of cancer

• Fig. 25.7

19
Normal cells versus cancer cells

• Table 25.1

20
Cancer a failure of genetic control contd.

• Proto-oncogenes
• Encode for proteins that promote the cell cycle
  and prevent apoptosis
• Mutations in proto-oncogenes result in oncogenes
  that promote cell division even more than
  proto-oncogenes do
• Results in over expression
• Oncogene activity causes cell to release large
  amounts of cyclin
• Results from mutation in cyclin-D proto-oncogene
• Causes cell signaling pathway to be constantly
  active and prevents apoptosis
• A proto-oncogene codes for a protein that makes
  p53 unavailable
• p53 transcription activator which stops cell
  cycle and promotes apoptosis

21
Mutations of proto-oncogenes

• Fig. 25.8

22
Cancer a failure of genetic control contd.

• Tumor-suppressor genes
• Mutations in tumor suppressor genes result in
  loss of function so products no longer inhibit
  cyclin nor promote apoptosis
• loss of function mutations
• Ex retinoblastoma protein controls transcription
  factor for cyclin D
• When tumor-suppressor gene p16 mutates, the
  retinoblastoma protein is always active
• Cell experiences repeated replications of DNA
  without cell division

23
Mutations of tumor-suppressor genes

• Fig. 25.9

24
Cancer a failure of genetic control contd.

• Other genetic changes
• Telomere shortening- sequences of bases at the
  ends of chromosomes that keep them from fusing
  together
• In normal cells, telomeres get shorter with each
  division and eventually the cell dies from
  apoptosis
• In cancer cells, telomerase enzyme rebuilds
  telomeres so divisions can continue
• Angiogenesis- tumor cells release growth factors
  that stimulate vessel and capillary growth to
  deliver nutrients and oxygen
• Metastasis- cancer cells break through basement
  membranes and enter blood and lymph vessels to
  spread throughout body

25
Cancer a failure of genetic control contd.

• Causes of cancer
• Heredity
• Some types of cancer run in families
• Carcinogens
• Environmental agents that are mutagenic
• Radiation, some viruses, organic chemicals

26
Cancer a failure of genetic control contd.

• Diagnosis of cancer
• Screening tests
• Pap smear, mammogram, colonoscopy
• Tumor marker tests
• Genetic tests
• Confirming diagnosis
• Biopsy, ultrasound, radioactive scans
• Treatment of cancer
• Chemotherapy
• Radiation therapy
• Bone marrow transplant
• Future- vaccines, anti-angiogenic drugs