1. Inquiry into Life Eleventh Edition Sylvia S. Mader
Chapter 25
Control of Gene Expression and Cancer
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2. 25.1 Control of gene expression
Diploid cells are totipotent
Contains all genes necessary to develop into entire organisms
Reproductive cloning shows that cells are totipotent
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 cont’d.
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 cont’d.
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 cont’d.
Gene expression in bacteria cont’d.
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 cont’d.
Gene expression in eukaryotes
Housekeeping genes- control essential metabolic enzymes or structural components that are needed all the time
Very little regulation because products are always needed
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 cont’d.
Levels of gene control in eukaryotes cont’d.
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 cont’d.
Levels of gene control in eukaryotes cont’d.
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 cont’d.
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 cont’d.
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 cell’s 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 cont’d.
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 cont’d.
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 cont’d.
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 cont’d.
Causes of cancer
Heredity
Some types of cancer run in families
Carcinogens
Environmental agents that are mutagenic, or can cause chromosomal mutations are Radiation, some viruses, organic chemicals

26. Cancer: a failure of genetic control cont’d.
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

27. Cancer cells
Fig