Cancer and Suppressor Genetics: PTEN Shows Promise

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Mythical Smoker

The effects of nicotine reinforced the myth of the harmless cigarette. The addictive effects put the smoker at the mercy of PAHs and other carcinogens. Image by Openclips

Our genes, the environment, and personal habits are interconnected in ways we do not readily perceive. The interconnections could not be any more poignant than in the mechanisms of carcinogenesis, itself.

While it was once believed that the onset of cancer was the direct result of exposure to carcinogens, the presently emerging paradigm paints cancer as a co-evolving antagonist-and-partner to life.

The Fable of Cancer and Cigarettes

In the 1970s, cancer was one of the leading causes of death throughout the western world. It was a time when the Marlboro cigarette man could be easily identified in magazines, newspapers, and television ads.

However, the romantic perception of the conquering hero(ine) needing a soothing smoke to cap off ‘the killing’ had molecular components.

As any of the dozens of xeno-molecular components of cigarettes enters into the blood stream, it induces an inflammatory response from our immune system. Not only does our body fight the foreign substances but also it will destroy them outright. However, the component(s) to cigarettes that alter our fight of foreign chemicals are the addictive, molecular components. Nicotine primarily forces the body to accept the onslaught of carcinogens.

To the human physiology, nicotine helps release dopamine into the brain by affecting and stimulating the reward centers. Dopamine is a naturally occurring neurochemical, and it will chemically and physically alter our perception – the ‘sexy’ image of the cigarette may not be too far off the mark. Through nicotine’s effects on the brain, we, unwittingly, put down our guard.

A More Scientific Story of Cancer: DNA and Foreign Molecules

The carcinogens found in cigarettes come, in part, from the incomplete burning of tobacco—the PAHs (e.g. benzopyrenes). These molecules disrupt DNA and induce the disease. Over time our DNA can become permanently damaged, if smoking is not ceased.

At that point, it cannot repair itself nor can it fight carcinogens. DNA contains genes that suppress tumors and their growth—one known to be at Chromosome 10.

Scientists do not currently completely understand how the protein came to be. However, scientists posit that the tumor suppressor at Chromosome 10 is a genetic trait we carry as a result of our evolutionary response to cancers. Cancer, the uncontrolled growth of unwanted cells, may have co-evolved with life. Recent work places cancer’s origins to early Earth history with Metazoic life forms some two billion years ago.

We see cancer cells throughout other phyla of Animalia, as well. Some researchers believe cancer are steps in the evolutionary ladder of life that failed to adapt.

Chromosome 10’s Tumor Suppression Capacity

Scientists discovered the capacity of the cell-altering properties of the gene in Chromosome 10 in the mid-1980s. The initial studies came from fruit fly experimentation in which the PTEN protein regulated cell growth and insulin secretion. From that point, researchers studied PTEN proteins in mammals and showed similar results (insulin could be regulated). Surprisingly, other researchers showed that PTEN may be linked to Autism Spectrum Disorders, and the wide range of findings spurred researchers onward.

Up until 2012, there were no definitive cancer results to report. However, in mid-2012, two different groups showed that transgenic mice (with extra copies of the PTEN gene) could suppress tumors. The studies opened the door to confirm that PTEN protein could regulate many different types of cell growth.

Perhaps, the results paint the PTEN enzyme as a miracle substance. (The tumor suppressor enzyme is a 403 amino acid sequence implicated in many forms of cancer that include, leukemia, prostate, melanoma, and breast cancer.)

Physical and Biochemical Understanding of PTEN

When a group of workers at the University of Wisconsin examined the PTEN enzyme, the resulting analysis showed the enzyme to need a stabilizing presence of another molecular agent(s). Whether there is a co-agent that facilitates the actions of the enzyme, it is unknown. Many biochemical entities (such as enzymes) function in the presence of a chaperones- molecules or atoms that allow enzyme to do its job. However, research has not proved the presence of molecular chaperone with PTEN, as yet. In other words, more results will follow.

The PTEN enzyme, if slightly altered, becomes useless to protect DNA from the effects of carcinogens like PAH. (The alteration of the PTEN enzyme may be a result of a prior PAH alteration of the DNA at Chromosome 10, as well.) The enzyme, like many proteins, is susceptible to damage from physiological changes. The susceptibility of PTEN is, in part, due to its chemical scaffolding or molecular structure. The molecule is long, almost gangly in some descriptions.

However, when a molecular entity is ‘susceptible’ to the slightest changes in its milieu (chemical surroundings), like PTEN, it is as if it were sitting on the top of a saddle point. The slightest change in chemical environment tips it into less useful state. Thus, in a nutshell, PTEN is an enzyme with a wide range of functionality that the stability of its chemical surroundings dictates.

Tumor Suppressor

The enzyme, also known as, PTEN is a target of continuous study as potential therapeutic agent. Copyright image by National Institutes of Health. All Rights Reserved.

PTEN as Therapeutic Agent

In cases where cancer has been found to exist, researchers have subjected the cancer cells to PTEN, and the tumors recede. Much unlike toxic chemotherapeutic agents, PTEN is naturally-occurring. It has been a long road of research-there have been close to 2000 various research papers on PTEN.

However, the long road may prove to make this agent costly; especially, given the agent’s lack of stability under normal physiology. The consolation to the research comes when considering that PTEN naturally fights cancer and stabilizes cell growth-it will have a bright future.

 

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