Cellular SuperVILLIAN

Introduction

This course was one of the most rigorous and informative that I have ever taken. When I enrolled in this course I had no doubt that I'd enjoy it. Being that cancer is one of the most leading causes of death in our society today, it can be extremely helpful to understand how it is caused in order to prevent it. This class has also shown me that just how many things that I do and interact with every day can possibly lead to the development of cancer. It has made me more aware of the things I eat, and the chemicals I expose myself to.

On a more personal note, a very important person in my life was diagnosed with breast cancer, not once but twice. Who is this person you ask?My grandmother. This also played a role in my enrollment in this course. If there was anything that I could learn that could prevent this from happening again or to anyone else in my family, I would do it. Thankfully she survived both diagnoses and is still in my life now.

The Outcomes Are Coming!

"Describe the six hallmarks of cancer."

1. Self-sufficiency in growth signals - This means that a cancer cell does not need outside signals from other cells to tell it to divide. It can make it's own growth signals, and for this reason, it's growth potential is limitless. It can and will continue to grow and divide.

2. Insensitivity to Anti-growth signals - In addition to creating its own growth signals, cancer cells become resistant to anti-growth signals that are usually released by cells within proximity to it. Normal cells would receive these signals and immediately stop dividing while cancer cells do not respond to them at all.

3. Evading Apoptosis - Apoptosis is programmed cell death. This usually occurs if there is unrepairable damage or mutations to DNA inside the cell. To avoid replicating this DNA the cell is destroyed. Cancer cells have the ability to ignore signals that tell it to die and avoid death while continuing to not only live, but grow and divide.

4. Limitless Reproductive Potential - In normal cells, telomeres shorten every time a cell divides to avoid replicating old DNA. When telomeres reach a certain length it is a signal for the cell to die. Cancer cells have the ability to continuous maintain the length of their telomeres which mean they never shorten, and the cell never dies. This allows the cancer cell to continously divide and create more cancer cells.

5. Sustained Angiogenesis - Like normal cells, cancer cells need blood vessels to supply oxygen and nutrients (cell food). However cancer cells can can release signals to the body that can trigger the growth of new blood vessels. With this ability cancer cells never "starve" to death and can continually, no matter where they are get nutrients and oxygen to grow and divide.

6. Tissue Invasion and Metastasis - With the uncontrolled growth and division of cancer cells comes their ability to break off and invade other parts of the body. This ability is known as metastasis. This can cause cancer to settle in other parts of the body, and begin growth there, sort of like an invasive species with no natural predators to stop them from taking over.

"Describe the six hallmarks of cancer."

"Explain the types of gene mutations possible and how these mutations can contribute to cancer formation"

1. Transitions: A type of point mutation in which a nucleotide is exchanged with a different nucleotide of the same type. (Purine such as A is exchanged with another purine, such as G.)

2. Transversion: A type of point mutation in which a nucleotide is exchanged with a different nucleotide of a different type. (Purine such as A is exchanged with a pyrimidine such as T.)

3. Insertions: A mutation that occurs when one or more nucleotides is added to a DNA sequence.

4. Deletion: A mutation that occurs when one or more nucleotides is added to a DNA sequence.

5. Chromosomal Translocations: When parts of a DNA sequence are rearranged between chromosimes that are not paired.

How do these mutations contribute to the cancer formation?

As these mutations build up in DNA , the DNA is replicated. If these mutations are not caught and fixed then these mutations will also be replicated.

"Describe an oncogene and why it is important in cancer development"

An oncogene is a gene that is responsible for the regulation of cell growth and division. This mutate gene up regulates proteins responsible for cell growth and division causing the cell to grow rapidly. If this gene somehow becomes mutated or malfunctions, it can lead to out of control cell growth or cancer. The mutation of this gene allows cells to continuously divide and quickly grow as they continuously replicate errors, create more errors and give rise to new cells that also have these errors if not more.

"Explain the cell cycle, its regulation, and how cell cycle dysfunction can lead to cancer"

The Cell Cycle is a series of stages a cell undergoes to divide. It consists of four stages which are M phase (Nuclear and cytoplasm division), G1 phase, S phase (DNA is replicated), and G2 phase.

Interphase: During this phase the cell becomes larger and makes replicates the DNA. Interphase consists of…

G1 Phase: G1 is considered the first gap phase, and is also where the cell itself physically increases in size, it makes more organelles, and also creates the molecules it will use later in the process.
S phase: In this stage the cell makes copies of its DNA.
G2 Phase: This is the second gap phase, where the cell grows more, continues to make more organelles, make proteins and prepare for mitosis.

Mitotic Phase (M Phase): The cell begins to divide its cytoplasm and separate is DNA creating two copies.

The cell’s nucleus disappears and the chromatin fibers in the cell coil tightly and become condensed.

Prophase

Centrioles can be seen at the opposite poles of the cell. Chromosomes are also lined up along the metaphase plate. The chromosome’s centromeres are all aligned. Chromatids are also attached to the spindles.

Metaphase

Paired chromosomes are separated, and pulled by the microtubule spindle towards each pole as they move apart. By the time, they are done pulling, each pole will possess a set of complete chromosomes.

Anaphase

The nuclei of the new daughter cells begin to form at the opposite poles, and nuclear envelopes are reformed. Chromatin also uncoils. This stage marks the competition of mitosis. The new nucleus of the daughter cell is genetically the same as the parent cell

Telophase

A cleavage furrow forms between the two potentially separate cells, which helps the new cell to pinch away from the original one. The cell then splits into a new cell, known as a daughter cell.

Cytokinesis

The cell cycle is regulated by a series of checkpoints and signals. These checkpoints allow the cell to take a minute to make sure everything is okay before it continues to divide. Upon passing these "checkpoints" the cell receives signals that tell it, it should go on a divide. If the cell does not pass a checkpoint, it will activate apoptosis which as stated earlier is programmed cell death. This apoptotic signal will tell the cell that something is wrong and it should "self-destruct". If the cell bypasses the checkpoint this can cause errors to be missed and the cell could replicate with errors. Also, the growth would be very quick and unregulated. The cell would be able to by-pass apoptosis if able to avoid checkpoints. This would allow the cell to become cancerous, and continue to produce other cancer cells.

"Describe the function of tumor suppressor genes"

Tumor suppressor genes are genes that essentially protects a cell from becoming cancerous. They do this by slowing down cell division so that the cell goes through all necessary checkpoints, repairing mutations and damage to DNA, and triggering apoptosis so that damaged cells with irreparable DNA do not divide to create more of themselves. If mutated, tumor suppressor genes can not regulate the cell cycle and division, which can lead to rapid cell growth, and later the development of a tumor.

"Explain how external and internal stimuli can lead to apoptosis"

Extrinsic Pathway

The extrinsic pathway used to tripper apoptosis from the outside of the cell uses a death receptor on the surface of the cell. A signal, known as a death factor binds to the death receptor. When this binding occurs, the receptor changes its shape and comes together with other receptors in an effort to relay the message inside the cell.
The change in shape causes an area known as a death domain located on the receptor to be exposed. Their exposure allows the binding of other proteins necessary for apoptosis to bind. These proteins then send the signal to caspases inside the cell which further carry out the process of apoptosis.

Intrinsic Pathway

Irreparable or too much DNA damage can trigger apoptosis from the inside of the cell. The use of the death receptors and binding proteins that trigger cell death from the outside of the cell are not needed.

"Clarify how cancer cells escape cell death"

In cases where tumor suppressor genes are mutated in the cancerous cell, cells can over produces proteins that ward off apoptosis such as IAP or survivin and Bcl2. These proteins keep caspases in check so caspase cascade can not occur and lead to apoptosis. Also with a malfunctioning tumor suppressor, gene this can cause death receptors usually found on the surface of normal cells to not be expressed on the surface of cancerous ones, which causes them to not be able to receive apoptotic signals from the cellular environment.

"List and describe the steps that lead to metastasis"

1.Invasion: Cancer cells do this by breaking away from their original tumor and leaving the area.

2.Intravasation: The cancer cell actually enters into a blood or lymphatic vessel.

3.Transport: The cancer cell travels via the blood stream or lymphatic system to other parts of the body. It essentially uses the body's systems to spread to other regions.

4.Extravasation: The cancer cell leaves the blood stream or lymphatic system to settle into a new part of the body. In this step the cancer cell is done transport and has found a place to exit and settle.

5.Metastatic colonization: In this final step the cancer cell "makes itself at home". It settles and begins to grow and divide.

"Give details on how chronic inflammation and infectious agents can lead to cancer"

Chronic inflammation can lead to the build-up of oxidants. These oxidants can damage a normal cell's DNA, causing a mutation. If cancer is in fact caused by inflammation, the cancer cells will create and release toxins that signal the body that there is something wrong that requires healing. This will cause more inflammation, creating more cancer cells. This also creates a blood supply (nutrients and oxygen) for the cancer cells. The nutrients and oxygen supplied by blood, "feed" the cancer cells and provide them with what they require to continue to grow. The blood supply also allows the cancer cell a mode of transportation to move about the body and wreck more havoc.

Some infectious agents cause cancer indirectly by causing chronic inflammation which then leads to cancer, and some integrate themselves inside the DNA of their hosts. Specifically Human Papillomavirus (HPV) causes out of control cellular proliferation by targeting p53 (one of the most important tumor suppressor genes) and disabling a cell's ability to activate apoptosis.

"Explain the role of diet in cancer development and prevention"

Antioxidants play a important role in cancer development because they prevent the buildup of oxidants in the body which can interact with DNA to cause damage and mutations. Eating charred foods from grilling also can cause DNA damage. These chemicals from charred foods are called Polycyclic Aromatic Hydrocarbons. They are indirect carcinogens, meaning that after they are metabolized in the body, they are then able to interact with DNA and cause damage.

References

All images are from Google Image.

All videos are from YouTube.

All assignments have their own lists of references.

Pecorino, L. (2008). Molecular Biology of Cancer. Oxford University Press.

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