LE 12-2b Growth and development 200 µm

LE 12-2c Tissue renewal 20 µm

Types of Cells ProliferationDifferentiation Highly differentiated cells: Quiescent cells: Highly mitotic cells:

How to determine the cycle?

LE 12-13a Experiment 1 S S S G1G1 When a cell in the S phase was fused with a cell in G 1, the G 1 cell immediately entered the S phase—DNA was synthesized.

LE 12-13b Experiment 2 G1G1 M MM When a cell in the M phase was fused with a cell in G 1, the G 1 cell immediately began mitosis—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 division neoplasm tumor invade neighboring tissue metastasis

LE 12-18a Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells

LE 12-18b Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. Cancer cells 25 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 Glandular tissue A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue.

LE 12-19b Cancer cell Blood vessel Lymph vessel Metastatic tumor Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may survive and establish a new tumor in another part 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: epithelial PDGF: platelet - derived CSF: colony stimulating FGF: basic fibroblast

Some Familial Cancers Rb familial polyposis coli Wilms Tumor familial breast cancer Li- Fraumeni familial cancer

EGF EGFR-P QuiescentCell Division P53 p53-p P21 CDK2-p21 Cyclin E CDK2 Cyclin E CyclinA Rb-p Rb ras fos Jun D-cyclin, CDK 2/4/6 Rb E2F Enzymes for DNA synthesis G1S

Figure Multiple nuclei 2.Lost adhesion 3.Irregular cell shape 4.Vessel invation Therapy: 1.Vessel growth inhibitor 2.Nucleotide analog

Figure 9.8a

Protection against cancer: 1.Apoptosis 2.Immunity 3.Telomeres

Cancer Protection Immunity Apoptosis normal increased growth adenoma I adenoma II adenoma III 5q gene loss ras mutation ch 18 loss carcinomametastasis ch 17 p53 other ch