Cell Division and Cancer

Cancer cells are cells gone wrong in other words, they no longer respond to many of
the signals that control cellular growth and death. Cancer cells originate within tissues
and, as they grow and divide, they diverge ever further from normalcy. Over time, these
cells become increasingly resistant to the controls that maintain normal tissue and as
a result, they divide more rapidly than their progenitors and become less dependent on
signals from other cells. Cancer cells even evade programmed cell death, despite the
fact that their multiple abnormalities would normally make them prime targets for
apoptosis. In the late stages of cancer, cells break through normal tissue boundaries
and metastasize (spread) to new sites in the body.

How Do Cancer Cells Differ from Normal Cells?

In normal cells, hundreds of genes intricately control the process of cell division. Normal
growth requires a balance between the activity of those genes that promote cell
proliferation and those that suppress it. It also relies on the activities of genes that signal
when damaged cells should undergo apoptosis.
Cells become cancerous after mutations accumulate in the various genes that control
cell proliferation. According to research findings from the Cancer Genome Project, most
cancer cells possess 60 or more mutations. The challenge for medical researchers is to
identify which of these mutations are responsible for particular kinds of cancer. This
process is akin to searching for the proverbial needle in a haystack, because many of
the mutations present in these cells have little to nothing to do with cancer growth.
Different kinds of cancers have different mutational signatures. However, scientific
comparison of multiple tumor types has revealed that certain genes are mutated in
cancer cells more often than others. For instance, growth-promoting genes, such as the
gene for the signaling protein Ras, are among those most commonly mutated in cancer
cells, becoming super-active and producing cells that are too strongly stimulated by
growth receptors. Some chemotherapy drugs work to counteract these mutations by
blocking the action of growth-signaling proteins. The breast cancer drug Herceptin, for
example, blocks overactive receptor tyrosine kinases (RTKs), and the drug Gleevec
blocks a mutant signaling kinase associated with chronic myelogenous leukemia.
Other cancer-related mutations inactivate the genes that suppress cell proliferation or
those that signal the need for apoptosis. These genes, known as tumor suppressor
genes, normally function like brakes on proliferation, and both copies within a cell must

be mutated in order for uncontrolled division to occur. For example, many cancer cells
carry two mutant copies of the gene that codes for p53, a multifunctional protein that
normally senses DNA damage and acts as a transcription factor for checkpoint control
genes.

How Do Cancerous Changes Arise?

Gene mutations accumulate over time as a result of independent events. Consequently,
the path to cancer involves multiple steps. In fact, many scientists view the progression
of cancer as a microevolutionary process.

Figure 1: Microevolution of a cancer cell

A series of mutations in a cell causes it to proliferate more than its immediate neighbors.
As the cluster of dividing cells grows over time, further mutations turn atypical
hyperplasia into a cancer (carcinoma). The spreading of cancer cells to other tissues
and organs (metastasis) occurs when the adhesion of these cancerous cells breaks
down, and they are able to travel easily to new locations.
2010 Nature Education All rights reserved.
Figure Detail

Figure 2
Figure Detail
To understand what this means, consider the following: When a mutation gives a cancer
cell a growth advantage, it can make more copies of itself than a normal cell can and
its offspring can outperform their noncancerous counterparts in the competition for
resources. Later, a second mutation might provide the cancer cell with yet another

reproductive advantage, which in turn intensifies its competitive advantage even more.
And, if key checkpoints are missed or repair genes are damaged, then the rate of
damage accumulation increases still further. This process continues with every new
mutation that offers such benefits, and it is a driving force in the evolution of living things
not just cancer cells (Figure 1, Figure 2).

How Do Cancer Cells Spread to Other Tissues?

During the early stages of cancer, tumors are typically benign and remain confined
within the normal boundaries of a tissue. As tumors grow and become malignant,
however, they gain the ability to break through these boundaries and invade adjoining
tissues.

Figure 3
Figure Detail
Invasive cancer cells often secrete proteases that enable them to degrade the
extracellular matrix at a tissue's boundary. Proteases also give cancer cells the ability to
create new passageways in tissues. For example, they can break down the junctions
that join cells together, thereby gaining access to new territories.
Metastasis literally meaning "new place" is one of the terminal stages of cancer.
In this stage, cancerous cells enter the bloodstream or the lymphatic system and travel
to a new location in the body, where they begin to divide and lay the foundation for
secondary tumors. Not all cancer cells can metastasize. In order to spread in this way,
the cells must have the ability to penetrate the normal barriers of the body so that they
can both enter and exit the blood or lymph vessels. Even traveling metastatic cancer
cells face challenges when trying to grow in new areas (Figure 3).

Conclusion

Cancer is unchecked cell growth. Mutations in genes can cause cancer by accelerating
cell division rates or inhibiting normal controls on the system, such as cell cycle arrest or
programmed cell death. As a mass of cancerous cells grows, it can develop into a
tumor. Cancer cells can also invade neighboring tissues and sometimes even break off
and travel to other parts of the body, leading to the formation of new tumors at those
sites.
eBooks
This page appears in the following eBook
Essentials of Cell Biology, Unit 5.5
Cell Biology for Seminars, Unit 5.5

http://www.nature.com/scitable/topicpage/cell-division-and-cancer-14046590

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.

For one-celled organisms, cell division = reproduction; each cell

division not only produces a new cell, it also produces a new organism
(bacteria, protists).
For multicellular organisms (like us) cell division allows an organism
to grow and develop from a single cell to trillions of cells, and also
to repair and replace 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

Growth of cell, development of organelles,
G1 making and breaking of macromolecules,
repairing wounds, sorting proteins, cellular

work. Also called "Gap 1".

Synthesis DNA replication - the cell
S makes a copy of each of its chromosomes,
in preparation for cell division (mitosis).
Growth (more) and more preparation for
G2
cell division. Also called "Gap 2".
Mitotis distribution of the replicated
M
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

Prophase

Chromosomes
condense

Draw me here:

Chromosomes
attach to
splindles Prometaphase
Nuclear
envelope
breaks down
Chromosomes
align on
Metaphase
themetaphase
plate (cell's
midline)
Chromosomes
separate pulled apart
Anaphase
into daughter
chromosomes
Chromosomes
relax. Nucleus
re-forms. Cell
Telophase
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.

Signs and symptoms of cervical cancer

Women with early cervical cancers and pre-cancers usually have no symptoms. Symptoms often do not
begin until a pre-cancer becomes a true invasive cancer and grows into nearby tissue. When this
happens, the most common symptoms are:

Abnormal vaginal bleeding, such as bleeding after sex (vaginal intercourse), bleeding after
menopause, bleeding and spotting between periods, and having longer or heavier (menstrual)
periods than usual. Bleeding after douching, or after a pelvic exam is a common symptom of
cervical cancer but not pre-cancer.

An unusual discharge from the vagina the discharge may contain some blood and may occur
between your periods or after menopause.

Pain during sex (vaginal intercourse).

These signs and symptoms can also be caused by conditions other than cervical cancer. For example, an
infection can cause pain or bleeding. Still, if you have any of these problems, you should see your health
care professional right away even if you have been getting regular Pap tests. If it is an infection, it will
need to be treated. If its cancer, ignoring symptoms might allow it to progress to a more advanced stage
and lower your chance for effective treatment.
Even better, don't wait for symptoms to appear. Be screened regularly.

Last Medical Review: 09/17/2014

Last Revised: 10/16/2014

http://www.cancer.org/cancer/cervicalcancer/moreinformation/cervicalcancerpreventionandearlydetec
tion/cervical-cancer-prevention-and-early-detection-cervical-cancer-signs-and-symptoms