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CancerSH1 H2 BiologyE-lecture (June Holidays 2014)

Colon Cancer cells

Prostate Cancer Cells

Lung Cancer Cells

Breast Cancer cell

Kidney Cancer Cells

+1. Introduction:How uncontrolled cell division results in cancer Cancer starts when a cell escapes the mechanisms that

normally regulate the cell cycle. It begins to divide in an uncontrolled way.

Benign tumour

Malignant tumour

+Metastasis of a primary malignant tumour

(Primary malignant tumour)

Carried via blood / lymphatic system to distant sites where they lodge and divide forming secondary tumours

+Basic characteristics of cancer cells

Do not stop dividing, virtually immortal until the body in which they reside dies. Independence from surrounding normal tissues, not responsive to signals. Undifferentiated (unable to carrry out any specialised function) Unresponsive to usual cell cycle controls.Cancer is a genetic disorder of somatic tissue, involves mutations of genes

encoding proteins that regulate cell cycle.

Pg 3

+2. The (normal) cell cycleCell cycle:

G1 (1st Growth) phase S (Synthesis) phase G2 (2nd Growth) phase Mitosis Cytokinesis

Regulated at certain critical times in cell cycle called: CheckpointsRegulated by 2 groups of proteins:

Cyclins Cyclin dependent

kinases (Cdks)

Pg 4

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THE CELL CYCLEPrimary (1st) growth phase

DNA replication

Second growth phase

Mitosis

Cytokinesis

Go

Pg 5 2. 1

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THE CELL CYCLEPrimary (1st) growth phase

DNA replication

Second growth phase

Mitosis

Cytokinesis

Go

Are mitogens present? (mitogens: signal (mitogens: signal molecules, usually molecules, usually proteins that proteins that stimulate cell stimulate cell division) division) Is the cell size big enough?

Have all the genes been replicated?

Are all the chromosomes aligned properly at metaphase plate?

(Metaphase (Metaphase checkpoint)checkpoint)

2. 2

+ Criteria to enter S phase:1.Is envt favourable? 2.Are mitogens present?3.Have you grown big enough?

+Defective spindle assembly (unattached kinetochores)Metaphase

X Cell cycle is arrested at metaphase

Possible result if mitosis was not stopped

Cell division

Missing chromosome Extra

chromosome

Metaphase checkpoint

+2.3 The cell cycle’s cyclin control system

Adds phosphate group to its substrate

ACTIVECdk

attached to a cyclin not phosphorylated not bound to its inhibitor

(Cdks are present at a constant concentration, but inactive most of the time)

(Cyclin concentration fluctuates cyclically)There are several types of cyclins.

Substrate becomes active / inactive

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+2.3 The cell cycle’s cyclin control system (eg. MPF –complex of mitotic cyclin + Cdk, MPF level increases during interphase and peaks at metaphase of mitosis)

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• As the cell cycle passes through the G1 and G2 checkpoints, Cdk becomes associated with different cyclins and, as a result, activates different cellular activities.

• At the completion of each phase, the specific cyclins are degraded, bringing Cdk activity to a halt until the next set of cyclins appears.

+3. Characteristics of Cancer Cells1. Loss of cell cycle control

2. Lack contact inhibition

3. Loss of cell death

4. Immortality due to activated telomerase gene activity

5. Less differentiated and less adherent

6. Ability to induce local blood vessel formation (Angiogenesis)

7. Ability to metastasize

8. Exhibit genomic instability

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+3. Characteristics of Cancer Cells1. Loss of cell cycle control

4. Immortality due to activated telomerase gene activity (similar to stem cells, but not present in normal somatic cells)

+3. Characteristics of Cancer Cells5. Less differentiated and less adherent

(Differentiated cells are cells that are specialised to serve a certain function, eg. skin cells, liver cells etc. They are specialised because they express a certain set of proteins required for their specialised function)

6. Ability to induce local blood vessel formation (Angiogenesis)

7. Ability to metastasize

+Animation: Growth of a tumour

Click on the picture to visit the site to watch the video!