Transcript Control of Gene Expression and Cancer

Inquiry into Life
Eleventh Edition
Sylvia S. Mader
Chapter 25
Control of Gene Expression and Cancer
25-1
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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
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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
++25-3
Two types of cloning
• Fig. 25.1
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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
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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
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The lac operon
• Fig. 25.2
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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
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X-inactivation in mammalian females
• Fig. 25.3
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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
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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
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Levels of gene expression control in
eukaryotic cells
• Fig. 25.4
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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
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Transcription factors and enhancers
• Fig. 25.5
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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
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Cell-signaling pathway
• Fig. 25.6
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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
++25-17
Development of cancer
• Fig. 25.7
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Normal cells versus cancer cells
• Table 25.1
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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
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Mutations of proto-oncogenes
• Fig. 25.8
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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
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Mutations of tumor-suppressor genes
• Fig. 25.9
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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
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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
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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
++ 25-26
Cancer cells
• Fig. 25.11
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