12 09 09 Lecture

11.18 Cancer results from mutations in genes that control cell division

Mutations in two types of genes can cause cancer

– Oncogenes

– Proto-oncogenes normally promote cell division

– Mutations to oncogenes enhance activity

– Tumor-suppressor genes

– Normally inhibit cell division

– Mutations inactivate the genes and allow uncontrolled division to occur

Copyright © 2009 Pearson Education, Inc.


Oncogenes

– Promote cancer when present in a single copy

– Can be viral genes inserted into host chromosomes

– Can be mutated versions of proto-oncogenes, normal genes that promote cell division and differentiation

– Converting a proto-oncogene to an oncogene can occur by

– Mutation causing increased protein activity

– Increased number of gene copies causing more protein to be produced

– Change in location putting the gene under control of new promoter for increased transcription



Tumor-suppressor genes

– Promote cancer when both copies are mutated


Mutation withinthe gene

Hyperactivegrowth-stimulatingprotein in normalamount

Proto-oncogene DNA

Multiple copiesof the gene

Gene moved tonew DNA locus,

under new controls

Oncogene New promoter

Normal growth-stimulatingprotein in excess

Normal growth-stimulatingprotein in excess

Mutated tumor-suppressor geneTumor-suppressor gene

Defective,nonfunctioningprotein

Normalgrowth-inhibitingprotein

Cell divisionunder control

Cell division notunder control

11.19 Multiple genetic changes underlie the development of cancer

Four or more somatic mutations are usually required to produce a cancer cell

One possible scenario for colorectal cancer includes

– Activation of an oncogene increases cell division

– Inactivation of tumor suppressor gene causes formation of a benign tumor

– Additional mutations lead to a malignant tumor


1

Colon wall

Cellularchanges:

DNAchanges:

Oncogeneactivated

Increasedcell division

Tumor-suppressorgene inactivated

Growth of polyp

Second tumor-suppressor geneinactivated

Growth of malignanttumor (carcinoma)

2 3

Chromosomes 1mutation

Normalcell

4mutations

3mutations

2mutations

Malignantcell

11.20 Faulty proteins can interfere with normal signal transduction pathways

Path producing a product that stimulates cell division

Product of ras proto-oncogene relays a signal when growth hormone binds to receptor

Product of ras oncogene relays the signal in the absence of hormone binding, leading to uncontrolled growth


11.20 Faulty proteins can interfere with normal signal transduction pathways

Path producing a product that inhibits cell division

– Product of p53 tumor-suppressor gene is a transcription factor

– p53 transcription factor normally activates genes for factors that stop cell division

– In the absence of functional p53, cell division continues because the inhibitory protein is not produced


Growth factor

Protein thatStimulatescell division

Translation

Nucleus

DNA

Target cell

Normal productof ras gene

Receptor

Relayproteins

Transcriptionfactor(activated)

Hyperactiverelay protein(product ofras oncogene)issues signalson its own

Transcription

Growth-inhibiting factor

Protein thatinhibitscell division

Translation

Normal productof p53 gene

Receptor

Relayproteins

Transcriptionfactor(activated)

Nonfunctional transcriptionfactor (product of faulty p53tumor-suppressor gene) cannot trigger transcription

Transcription

Protein absent(cell divisionnot inhibited)

11.21 CONNECTION: Lifestyle choices can reduce the risk of cancer

Carcinogens are cancer-causing agents that damage DNA and promote cell division

– X-rays and ultraviolet radiation

– Tobacco

Healthy lifestyle choices

– Avoiding carcinogens

– Avoiding fat and including foods with fiber and antioxidants

– Regular medical checkupsCopyright © 2009 Pearson Education, Inc.

Effects of a growth factor at the G1 checkpoint

– A growth factor binds to a receptor in the plasma membrane

– Within the cell, a signal transduction pathway propagates the signal through a series of relay molecules

– The signal reaches the cell cycle control system to trigger entry into the S phase

8.9 Growth factors signal the cell cycle control system


G1 checkpoint

Controlsystem

M

S

G2

G1

Receptorprotein

Signaltransductionpathway

Relayproteins

Plasma membrane

Growth factor

Cancer cells escape controls on the cell cycle

– Cancer cells divide rapidly, often in the absence of growth factors

– They spread to other tissues through the circulatory system

– Growth is not inhibited by other cells, and tumors form

– Benign tumors remain at the original site

– Malignant tumors spread to other locations by metastasis

8.10 CONNECTION: Growing out of control, cancer cells produce malignant tumors


Cancer treatments

– Localized tumors can be treated with surgery or radiation

– Chemotherapy is used for metastatic tumors



Classification of cancer by origin

– Carcinomas arise in external or internal body coverings

– Sarcomas arise in supportive and connective tissue

– Leukemias and lymphomas arise from blood-forming tissues



A tumor grows from asingle cancer cell.

Cancer cells spreadthrough lymph andblood vessels toother parts of the body.

Cancer cells invadeneighboring tissue.

Tumor

Glandulartissue

Lymphvessels

Bloodvessel

What a cancer cell has to do in order to be successful:

1.) Disregard cell signaling that regulates proliferation.

2.) DO NOT BE SUCICIDAL (abort apoptosis)

3.) Avoid differentiating and replicative senescence.

4.) Be genetically unstable.

5.) Escape! Good at getting out of the home tissue.

6.) Survive and grow in foreign sites (Metastasize)

Technology

12 09 09 Lecture