25-1

Inquiry into LifeEleventh Edition

Sylvia S. Mader

Chapter 25Control of Gene Expression and Cancer

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

25-2

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

++25-3

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

25-4

Two types of cloning

• Fig. 25.1

25-5

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

25-6

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

25-7

The lac operon

• Fig. 25.2

25-8

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

25-9

X-inactivation in mammalian females

• Fig. 25.3

25-10

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

25-11

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

25-12

Levels of gene expression control in eukaryotic cells

• Fig. 25.4

25-13

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

25-14

Transcription factors and enhancers

• Fig. 25.5

25-15

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

25-16

Cell-signaling pathway

• Fig. 25.6

++25-17

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

25-18

Development of cancer

• Fig. 25.7

25-19

Normal cells versus cancer cells

• Table 25.1

25-20

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

25-21

Mutations of proto-oncogenes

• Fig. 25.8

25-22

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

25-23

Mutations of tumor-suppressor genes

• Fig. 25.9

++ 25-24

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

++ 25-25

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

++ 25-26

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

25-27

Cancer cells

• Fig. 25.11