Cell Reproduction: Mitosis and Cancer
February 14, 2000


Readings: Starr text: Ch 8 cover page, 8.1 - 8.4, 8.6 -8.7
CD-ROM: excellent diagrams and a cool mitosis movie!
News Page and Experiments page:


"To understand the things that are at our door is the best preparation for understanding those things that lie beyond"
- Hypatia, c. 370-415

 Outline: Cell Reproduction: Mitosis and Cancer

I. Cell Division overview
II. The Cell Cycle
II.Mitosis - how 1 cell divides into 2
IV. Stages of Mitosis
V. Cancer cells

I. Cell Division

Life is based on the ability of cells to reproduce, or make copies of themselves. This is done by a process called cell division = one cell divides into two cells.

Somatic Cells: (Ch 8 - today) body cells of an organism that do all the 'daily' functions of the organism

Germ Cells: (Ch 9 - Wednesday) reproductive cells - eggs and sperm

 

II. The Cell Cycle:

A cell spends a good part of its "life" working and growing, breaking down sugars, making ATP, synthesizing proteins, enzymes, and other macromolecules.

At other times, the cell makes preparations for reproduction, or cell division, where 1 cell will divide to form 2 "daughter" cells, and the whole process will start over again!

 

Phases of the Cell Cycle

G1 Growth of cell, development of organelles, making and breaking of macromolecules, repairing wounds, sorting proteins, cellular work. Also called "Gap 1".
 S Synthesis ­ DNA replication - the cell makes a copy of each of its chromosomes, in preparation for cell division (mitosis).
 G2 Growth (more) and more preparation for cell division. Also called "Gap 2".
 M Mitotis distribution of the replicated chromosomes to two cells

 

Chromosomes: are found in the nucleus of cells and are made of DNA - repeating sequences of bases (A,T,C,G) - coiled tightly around histone proteins. An individual chromosome is one, l...o...n...g... DNA molecule which is highly coiled and condensed. The total number base pairs in all the chromosomes ONE human cell is approximately three billion (3,000,000,000); individual chromosomes range from 30 to 150 million base pairs EACH.

Humans have 46 chromosomes, (really 23 pairs of chromosomes, one originally from mon and one from dad). Each chromosome contains a few thousand genes, that "code for" all cellular proteins.

 

Diploid: indicates that our body cells have 23 pairs of chromosomes - and every time our body cells reproduce, each NEW cell must also end up with 23 pairs of chromosomes. We will discus this today.

Haploid: indicates that a cell has only ONE copy of each chromosome - this is necessary for the process of sexual reproduction. A human egg is haploid (has 23 chromosomes) and a sperm is haploid (has 23 chromosomes). Upon fertilization, the new baby now has the 'correct' human number of 46 chromosomes in each of its somatic cells. We will talk about this Wednesday.

 

III.Mitosis: how 1 cell divides into 2 identical cells

Cells do not just divide randomly into two cells during cell division; they must also distribute an exact copy of each of their chromosomes to each new cell.

Why the need to be so precise? Each chromosome contains thousands of genes, each necessary to the proper functioning of the organism. It is vital that each new cell gets the same set of chromosomes that its parent cell once had!

Humans have ~120,000 genes spread over 46 chromosomes in EACH ONE of our somatic (body) cells. EACH ONE of these cells is genetically indentical to each other.

 

Obviously, some SERIOUS organizational skills are needed to make sure this process runs smoothly......

A cell first prepares to go through mitosis by first making a copy of its all of its DNA (in S phase), so that each new cell can receive a complete set of chromosomes.

After S phase, each replicated chromosome is then composed of two identical parts - each copy of DNA is called a sister chromatid, held together by a centromere. The chromatids need to stay together to keep things "organized" in the cell.

Before DNA Replication (S Phase) - A chromosome


After DNA Replication - a duplicated chromosome, made up of 2 sister chromatids

 

The sister chromatids are pulled apart during mitosis (division of the nucleus), and partitioned into the 2 new daughter cells by cytokinesis (division of the cell).

Result of mitosis: two daughter cells genetically identical to the parent cell.

 

IV. Stages of Mitosis:

 Prophase: Chromosomes condense

 Prometaphase: Chromosomes attach to spindle

 Metaphase: Chromosomes align

 Anaphase: Chromosomes separate

 Telophase: Chromosomes relax

 The end result of mitosis = 2 indentical daughter cells

   What happens  Draw me here:
Prophase Chromosomes condense

 

 

 

 

Prometaphase Chromosomes attach to splindles - Nuclear envelope breaks down

 

 

 

 

Metaphase Chromosomes align on the metaphase plate (cell's midline)

 

 

 

 Anaphase Chromosomes separate - pulled apart into daughter chromosomes  
 Telophase Chromosomes relax. Nucleus re-forms. Cell pinches in two (cytokinesis)  

 

 

V. Cancer cells escape from the controls on cell division:

1. What is cancer? Cancer is essentially a disease of mitosis - the normal 'checkpoints' regularing mitosis are ignored or overriden by the cancer cell. Cancer begins when a single cell is transformed, or converted from a normal cell to a cancer cell. Often this is because of a change in function of one of several genes that normally function to control growth. (ie. the cell cycle gene p53, the "guardian of the genome" that is mutated in over 50% of all human cancers) or supress tumor formation (ie the "Breast Cancer Gene" BRCA 1) .

Once these crucial Cell Cycle genes start behaving abnormally, cancer cells start to proliferate wildly by repeated, uncontrolled mitosis.

Unlike normal cells, cancer cells ignore the usual density-dependent inhibition of growth, multiplying after contact with other cells are made, piling up until all nutrients are exhausted.

 

2. Tumors - Good Cells gone Bad...? The cancer cells proliferate to form mass of cancer cells called a tumor. As the tumor grows larger, it begins to release proteins from the cell to attract new blood vessel growth (this is called "angiogenesis"). At point the tumor contains ~ 1 million cells and is about the size of a 'bb'.

Benign: tumor cells remain at original site.

Malignant: some tumor cells send out signals that tell the body to produce a new blood vessel at the tumor site. These cells not only have a food and oxygen supply, they also have an avenue for escape to a new part of the body - through the new blood vessel and into bloodstream. Cells that break away from the tumor begin to spread to surrounding tissues (via the bloodstream or lymph) and start new tumors = metastasis.

 

3. Unusual features of Cancer Cells.

Cancer cells are frequently "immortal": whereas normal cells divide about 50 times and them die, cancer cells can go on dividing indefinitely if supplied with nutrients (See essay on HeLa cells ­ a cancer cell line used in cancer research that has been growing since 1951).

Cancer cells often have unusual numbers of chromosomes or mutations in chromosomes. Aging (production of toxic oxygen "free radicals"), exposure to toxins (like components of tobacco), mutagens (like ultraviolet light) all cause mutations in genes, but normal errors in DNA replication can lead transformation of the cell if they occur in a crucial gene.

Cancer cells may also have an abnormal cell surface; instead of "sticking" to its neighboring cells, cancer calls tend to "round up" and break attachments its neighbors cells, allowing for metastasis.

 

 

 Learning Objectives: After this lecture, your should be able to:

1. Draw or describe the phases of the cell cycle (and what happens in each)
2. Describe a chromosome and contrast it with a sister chromatid.
a. How did it get to BE a sister chromatid?
b. Why do the sister chromatide stay joined together?
3. Draw and describe each phase of mitosis (you will see this again, hint hint...)
4. Describe how a cell can be transformed into a cancer cell, and the unusual features of cancer cells.