The Cell Cycle & CancerQuestions we will try to answer

1. What is cancer?

2. How are cancerous cells different than normal cells?

3. How do you get cancer?

i.e. What makes normal cells become cancer cells?

What is cancer?

• Cancer is …

• Cancer cells cannot stop dividing

• Cell cycle

Fig 8.7

The Events of the Interphase

• Interphase:

• Divided into 3 phases:G1 –

S –

G2 –

• Length of G1 can vary greatly:

Cell Division or “M” phase

• Cell Division consists of two parts

1. Mitosis:

2. Cytokinesis:

• What needs to happen to the chromosomes prior to Mitosis?

• During mitosis?

Fig 8.6

Each chromatid has one DNA molecule

Centromere

Sister chromatids

1. How do sister chromatids compare genetically?

2. What happens to sister chromatids during mitosis?

Sketch of one duplicated chromosome

Mitosis: sister chromatids separate

Two-chromatidchromosome

Interphase

S-Phase: DNA Replication

One-chromatidchromosome

One-chromatidchromosome

Mitosis: Division of the Nucleus

• Four Stages:1. Prophase –

2. Metaphase –

3. Anaphase –centromeres break and the chromosomes (now single chromatids) migrate to opposite poles

4. Telophase – nuclear envelope forms around each cluster of chromosomes

Fig 8.8

Cytokinesis: division of the cytoplasm to create 2 new cells

Fig 8.9

• Mitosis

– Produces somatic (body) cells

• Meiosis– produces gametes

Fig 8.14

Normal Karyotype of Human

Chromosomes

• Karyotype =

• How many pairs of chromosomes in this Karyotype?

• Paired chromosomes are homologous

• How do you inherit chromosomes?

• What gender?• Sex vs. autosomal

chromosomes?

Sex chromosomes determine a person’s gender

• Humans have 46 chromosomes:

• Sex chromosomes:

Diploid cell: 6 total chromosomes, 3 sets of

homologous chromosomes

One set ofnon-homologouschromosomes

Haploid cell

One set of non-homologous

chromosomes

Haploid cell

Regulation of Cell Division

• What evidence in your own life do you have that cell division is regulatedby your body?

• What normally controls cell division?

Contact Inhibition

• Cells do not normally grow or divide when in contact w/ other cells

Contact inhibition does not occur in Cancerous Cells

• Cancerous cells continue growing and moving when they touch other cells.

Fig 8.10

Cell cycle control

Growth control in a normal cell

Signaling cellGrowth factor =

Growth factor binds to receptor

Receptor sets off a signal

cascade to nucleus

target cell entersS-phase and

divides,eventually

repairing wound

target cell

Nucleus

1. Cell might produce its own growth factor

Several ways to get faulty growth control in a cancer cell

2. Mutant receptor might turn on even withoutbinding growth factor

3. Signal cascade might occur even without triggerfrom receptor

The genetic basis of cancer (p.224-227 in Ch 11)

• Proto-oncogenes:

• Oncogenes: – genes that cause cancer

• Oncogenes are rarely inherited.....Why?

Tumor Suppressor Genes

• Tumor Suppressor Genes

• One mutant Tumor Suppressor Gene does not cause cancer....Why?

Fig. 11.20

BRCA 1: Breast Cancer Susceptibility Gene

• BRCA 1 is ….

• If a women inherits a mutant BRCA 1 she has a

– 80 to 90% chance of developing breast cancer– Why aren’t the percentages 100%?

• Why are the percentages (10%) much lower for the average woman?

Environmental causes of cancer

1. Viruses

2. Chemicals

3. Radiation

**All can cause mutations in tumor-suppressor genes and proto-oncogenes

Characteristics of all cancer cells

1. Immortal

2. Altered cell membranes

3. Have lost the genetic ability to stop dividing

4. Cancer is heritable:

5. Are dedifferentiated

6. No contact inhibition

7. If not treated will eventually cause death

Cancer treatment: Attack Actively Dividing Cells

• Three treatments for cancer:

1. Surgery

2. Radiation

3. Phase-specific chemotherapies

Phase-specific Chemotherapies

1. Prevent cells from entering the S-phase

2. Block the S phase

3. Block or stop mitosis

But chemotherapy can’t discriminate between cancer cells and normal cells….

• May affect all rapidly dividing cells• Which cells divide rapidly?

• So.... what would be the side effects?

Side Effects of Chemotherapy

How to lower your Cancer Risks

• Eat plenty of fiber– Fiber speeds passage through digestive tract

• Do not smoke• Drink alcohol in moderation or not at all• Exercise regularly• Do not become overweight• Limit dietary fat• Limit sun exposure or use sunscreen• Learn to recognize the warning signs of cancer

Common Warning Signs of Cancer: C.A.U.T.I.O.N.

C - change in bowel or bladder habits

A - a sore that does not heal

U - unusual bleeding or discharge

T - thickening or lump in the breast or any part of the body

I - indigestion or difficulty swallowing

O - obvious change in a wart or mole

N - nagging cough or hoarseness

Down Syndrome - Incidence with Mother’s age

• 1 in 1000 births in U.S. • 1 in 12 births for moms that are 50 years old• Most frequent genetic cause of mental

retardation – I.Q. = 20-50

Down Syndrome as function of mother’s age – Fig 8.23

Human Somatic Cells have 46

Chromosomes

• How many chromosomes in human gametes?

Down Syndrome

Meiosis

Down Syndrome Karyotype

• What is wrong with the Karyotype?

• Why are most trisomies fatal? (except sex chromo’s)

Human Life Cycle

• Meiosis

• What if gametes were made by mitosis?

Fig 8.14

Fig 8.15

Fig 8.16 Meiosis I

Stages of Meoisis1. Interphase –

2. Meiosis I

a) Prophase I –

b) Metaphase I –

c) Anaphase I –

d) Telophase I –

3. Meiosis IIa) Prophase II – chromosomes attach to spindleb) Metaphase II – chromosomes align at equatorc) Anaphase II – sister chromatids separated) Telophase II – cells divide, end result = 4 haploid

daughter cells

Normal Meiosis• How do the chromo’s

align at metaphase I?

• What separates at anaphase I?

• How do the chromo’s align at metaphase II?

• What separates at anaphase II?

diploid

Interphase

Meiosis I

Meiosis II

n

2n

n

nn

nn

Fig 8.17

Normal Meiosis followed by Fertilization

Meiosis I Meiosis II Product ofmeiosis

FertilizationZygote

Normal sperm

Normal diploidzygote

Chromosomes:

Both daughter cellshave one copy of

each chromosome

Nondisjunction:- in Meiosis I:

- Or

- In Meiosis II:

Genetic Basis of Down Syndrome:

Fig 8.20

Age of Mom vs. Age of Dad

• Why is the age of the mother, but not the father, correlated with the probability of having a child with Down Syndrome?

Egg formation in humans

• Pre-egg cells present before girls are born -- about 1000 or so.

• Pre-egg cells are stuck at metaphase I

• Ovulation:

Mom’s Pre-egg Cells form Prenatally

• Half of you was present inside your grandmother as a single cell inside your mom when she was a fetus.

• At about 12 years, women start ovulating one egg each month for next 40 years.

• So …..A 50 yr old woman has had her eggs sitting with chromosomes aligned in metaphase for over 50 years!

• Nondisjunction is rarely seen with chromosomes larger than #20--Why?

.

Why doesn’t the age of the father influence the rate of Down syndrome?

• Sex cell formation in Males:

Genetic Screening for Down Syndrome

• Can we detect D.S. before birth? • Amniocentesis: fetus located using ultrasound, needle

inserted and amniotic fluid extracted– Fluid contains fetal urine and fetal cells from skin,

respiratory tract, urinary tract– Make karyotype to detect abnormal chromosome

numbers.• Not performed until 16th week of pregnancy

Chorionic Villus Sampling (CVS) • Catheter inserted vaginally and chorionic

tissue removed• 9-11 weeks after conception results of

tests within days rather than weeks as in amniocentesis

• But may be slightly riskier for fetus

Meiosis Causes Genetic Variation

1. Independent Assortment– =

– Thus maternal and paternal chromosomes are shuffled

– 223 or 8,388,608 different possibilities from each parent, then fertilization gives 70 trillion

Fig. 8.18

2nd Reason for Genetic Variation

2. Crossing over

– Result:

Fig 8.19