LE 12-2b

Growth and development

200 µm

LE 12-2c

Tissue renewal

20 µm

Types of Cells

• Proliferation Differentiation

• Highly differentiated cells:

• Quiescent cells:

• Highly mitotic cells:

How to determine the cycle?

LE 12-13aExperiment 1

S

S S

G1

When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized.

LE 12-13bExperiment 2

G1M

M M

When a cell in the M phase was fused with a cell in G1, the G1 cell immediately beganmitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

Mitosis and Cancer

• Common and severe

• Some form strikes 1/3; 20% death; 20% health care costs

• Not a single disease

• Early detection and treatment is vital

cell divisionneoplasmtumor

invadeneighboring tissue

metastasis

LE 12-18a

Cells anchor to dish surface anddivide (anchorage dependence).

When cells have formed a completesingle layer, they stop dividing(density-dependent inhibition).

If some cells are scraped away, theremaining cells divide to fill the gap andthen stop (density-dependent inhibition).

25 µmNormal mammalian cells

LE 12-18b

Cancer cells do not exhibitanchorage dependenceor density-dependent inhibition.

Cancer cells25 µm

The genetic nature of cancer

• The clonal nature of cancer– Analyzing the cancer and normal cells– Most happen later in life

• Proto-oncogenes and oncogenes

• Recessive oncogenes and tumor suppressor genes

LE 12-19a

Tumor

Glandulartissue

A tumor grows from asingle cancer cell.

Cancer cells invadeneighboring tissue.

LE 12-19b

Cancer cell

Bloodvessel

Lymphvessel

Metastatictumor

Cancer cells spreadthrough lymph andblood vessels toother parts of thebody.

A small percentageof cancer cells maysurvive and establisha new tumor in anotherpart of the body.

Searching for Oncogenes

• Cell cycle regulatory genes

• A lot of cancer are associated with DNA virus

• Some cancers are familial

• In vitro mutagenesis on cultured cells

• Loss of heterozygocity

Some Oncogenes• Both viral AND cellular

• src (Rous sarcoma v.): Prototype of a family of membrane associated tyrosine kinases– over expressed or activated in cancer

Kinases: abl (abelson murine leukemia v.)trk (human colon carcinoma v.)

GTPase: ras (rat sarcoma v.)Transcription factors: fos, myc (chicken sarcoma v.)EGF: erb A (avian erythroblastosis v.)

EGF: epithelialPDGF: platelet - derivedCSF: colony stimulatingFGF: basic fibroblast

Some Familial Cancers

• Rb

• familial polyposis coli

• Wilms Tumor

• familial breast cancer

• Li- Fraumeni familial cancer

EGF

EGFR-P

Quiescent Cell Division

P53 p53-p

P21

CDK2-p21Cyclin E

CDK2Cyclin E

CyclinA

Rb-pRb

ras

fosJun

D-cyclin, CDK 2/4/6

RbE2F

E2FEnzymes for DNA synthesis

G1 S

Figure 9.71. Multiple nuclei2. Lost adhesion3. Irregular cell shape4. Vessel invation

Therapy:1. Vessel growth inhibitor2. Nucleotide analog

Figure 9.8a

Protection against cancer:

1. Apoptosis2. Immunity3. Telomeres

Cancer Protection

• Immunity

• Apoptosis

normalincreased growth

adenoma I adenoma II adenoma III

5q gene loss ras mutation ch 18 loss

carcinoma metastasis

ch 17

p53

other ch