BIO Special Lecture: Cancer and p53 Gene

This is a post from one of my other blogs that I made last year. While the MCAT does not directly test what causes cancer at the cellular level, I figured that this could be helpful if the topic did pop-up in a verbal passage or was maybe even mentioned in a biology passage testing your experimental knowledge (i.e. DNA microarrays and cDNA via reverse transcriptase). Please note that this writing was not intended for us future doctors; therefore it is slightly oversimplified at times but the underlying concepts are what's important. Enjoy

Killing more than 7.6 million people in 2007, cancer is the second leading cause of death in the world. In fact, half of all men and one third of all women will develop some type of cancer during their lifetimes. I recently took a Genetic Analysis class in college where there was a heavy emphasis on understanding what causes cancer at the cellular level and how treatments vary upon what we discover about the cancer (i.e. chemotherapy vs. surgery, etc.). I found this information to be overwhelmingly useful as an increasing number of my relatives have been diagnosed with some type of cancer in recent years. It's also shocking how little they know about the inner workings of this disease and how their doctors have arrived at their prognoses.

To preface what I am about to share with you, I think it is important to first define what cancer is. The American Cancer Society says that cancer results when cells in a part of the body begin to grow out of control. This definition is entirely true but I would like to clarify a little bit before we go any farther. First, most human cells are frequently replaced and reproduced during our life in order to protect us from cells that become too old and carry mutations. Mutations are changes in the base pair sequence of our DNA and are almost always deleterious to humans. So how do we get mutations? Mutations can result from copying errors during cell division or from carcinogens like tobacco smoke or radiation--hence what all smokers and frequent sun bathers have in common. Because our cells are frequently dividing, the older a cell gets the more prone it is to carry harmful mutations--this is because it has been constantly dividing and creating new cells for the body. Lucky for us, the body has the ability to distinguish between old and new cells, much like how it is able to differentiate between a healthy cell and a virus. WARNING: it's about to get more scientific. Our body is able to distinguish between old and new cells by measuring the telomeres of each cell which are located at the ends of the DNA. Telomeres are buffers that keep the DNA from being degraded every time it is replicated. For this part of our discussion, picture DNA as a long strand that contains a telomere at each end. Now every time our cell divides to make a new cell, the telomeres get shorter (the reason for this is complicated and beyond the scope of this post). Thus, as a cell keeps dividing and becomes older, the telomeres are shortened and will eventually be detected by the body. Once a cell is deemed hazardous (meaning the telomeres are too short and the cell is thus, too old), the targeted cell will actually undergo a programmed cell death called apoptosis. This is how our body protects us, by killing off the potentially harmful cells. HOWEVER, if a cell is cancerous (meaning the cell's DNA has multiple mutations), there is an interference with apoptosis so the cell continues to divide unregulated and uncontrollably--this is what the ACS meant when they said that cancer cells grow out of control. Because there is no regulation of the cell's life span via apoptosis, the cancer cells continue to divide and possibly spread around the body to vital organs (this will be later discussed in my benign vs. malignant tumor post).

So here are some takeaways:
-Cancer is cell division gone terribly wrong
-Cancer is fundamentally a disease of the genes
-Cancer is caused by mutations which can result from copying errors during cell division or from environmental carcinogenic agents like radiation and tobacco smoke--for our MCATers, multiple defects contribute to cancer. They are: cell division and differentiation, apoptosis, telomere erosion, contact inhibition, angiogenesis.
-The shortening of telomeres will trigger apoptosis (cell death) unless the cell is cancerous

One last note: for those of you who have had either biochemistry or a heavy dose of genetics are probably wondering why I failed to mention p53 and its role. Well here it is, compliments of my biochem text: The tumor suppressor gene p53 is found to be mutated in at least half of all human tumors. The level of p53 in the cell is controlled by its rate of degradation--this is because it is ubiquinated and targeted for destruction, like cyclins. Therefore, the concentration of p53 increases when its degradation is slowed. Activated p53 stimulates the synthesis of a protein that inhibits cyclin-dependent kinases, thereby block progression in the cell cycle. This regulatory mechanism would conceivably buy time for the cell to repair DNA using enzymes whose synthesis is also stimulated by p53. Some of p53's other target genes encode proteins that carry out apoptosis. Lastly, the position of p53 at the interface of pathways related to DNA repair, cell cycle control, and apoptosis indicate why the loss of the gene is so strongly associated with the development of cancer.