Cancer Cells: No Age Limits - Research Paper Example

dyeninapey Academia-research 7 May, Cancer Cells: No Age Limits The Difference Lies With Aging Why do cells become cancer cells? To answer the question and pose a hypothesis, we must first understand the fundamental difference between normal and cancer cells: cancer cells do not mature, do not age, and do not undergo cell death like normal cells do. Aging is the deterioration of functions over time, which, especially when an organism is not yet fully developed, usually comes with specialization on other functions. However, even if an organism has reached its development peak, the dwindling of physiological functions continue, until it reaches the endpoint, senescence. For multicellular organisms such as plants and animals, aging is a visible process. As a female child ages into a woman, the hips gradually become broader to permit the mature female to carry the growing fetus in her womb. The breasts become well-developed to allow her to provide the best nutrition possible once she delivers the conceived child. And since each multicellular organism is a composite of many cells, what we see happening to it is a reflection of what is happening inside the body, within the cells. The aging process of a multicellular organism such as a human is a reflection of division, development, and programmed cell death of its somatic cells. For a cell, the earliest physiological process to disappear once it is developing is its ability to produce daughter cells. Because once a cell is developing, it steps out of the cell cycle and enter a nondiving state, the Go phase. Most of the cells in a developed human body are in Go. Most common examples of these are the specialized neurons, which do not divide (Campbell and Reece, 2002, p. 226). So on the onset of life, a fertilized egg cell divides into many, and will be grouped according to what their functions will be once they develop defining characteristics that make them different from others. However, normal cells cannot multiply forever. Not only will development not permit them, as is the case once a cell dies before the organism, but mortality is engraved in the DNA. Since DNA replication mechanism only makes a daughter strand by adding nucleotides at the 3’ end, its 5’ end, which an RNA primer filled during the course of DNA replication, is left unfilled once the primer is removed, and the resulting DNA is shorter after every replication. The good thing is, the 5’ ends of DNA strands, called telomeres, do not actually code for a gene and are thus dispensable. But since telomeres are of defined length, DNA replication and cell division can only go through a defined number of cycles as well (Campbell and Reece, 2002, pp. 299-300). For humans, mitosis takes place in 1016 magnitude. For smaller organisms such as mice, cells divide at 1012 times per lifetime (Gilbert, 2003, p. 143). Many cells, however, undergo cell death even before the organism dies, so that the resulting developed organism can have the right number and types of cells at the right places around and within the body. For example, the cells making up the tissues between our digits had died even before we were born to give us five fingers on each hand. Other results of programmed cell death include the space at our middle ear where sound waves reverberate, and the orientation and proper spacing of neurons that transmit signals to and from the brain (Gilbert, 2003, p. 143). Indeed, on the molecular level, one of the most glaring evidences of development, even for cells that are destined to die earlier than the organism, is the transcription of genes that were not transcribed before, and expression of proteins that were not produced before. Cancer Kills Proteins are one of the pillars of a cell, and are the most diverse class of biomolecules. They are on the forefront of cell physiology. They can be structural, such as collagen and elastin, metabolic and catabolic, such as phosphatases and kinases, and can be a mode of transport, such as aquaporins. Some proteins can act as signal transducers that instruct a cell how to behave, when to divide, when to develop, or when to self-destruct. For normal cells, there are no problems coming up with the right combination of molecules needed for cell death or differentiation. It is logical to think that the problem with cancer cells is that they could not produce the proteins that will trigger the cascade of events leading to cell death and differentiation. Thus, it is the hypothesis of this review that “Mutations on genes encoding proteins that are the backbone of physiological processes underlying cell apoptosis and regulation of cell division causes cancer.” It is most likely that, for cancer cells, mutations in certain genes coding for a protein essential to stop cell division and promote cell death prevents the cell from producing that protein, and from stopping the abnormal cells to divide. That may sound harmless at first, but upon realizing that more often than not normal cells are around perpetually dividing cells, that normal cells do not divide in proportion to these abnormal cells, and that, because the cancer cells are alive and recognized by the body as a part just like any other, which needs to take in nutrients, a part of blood will be redirected to the area of cancer cells. How much blood will be redirected is a function of how big the mass of cancer cells is. Soon after, the blood circulating in the body will not be enough to effectively provide supplies and drain wastes. The body cannot bring the immune system to act against cancer cells because these abnormally propagating cells are still acknowledged as cells that has the same genetic material as the normal cells. To start, this review tackles the normal proceedings when it comes to cell cycle and apoptosis. The focus will then shift to the possibilities of what will happen once mutations on proteins that are important to cell cycle and apoptosis occur. The actuality of these possibilities will then be verified using previous studies that will be briefly discussed in this review. For so many years, cancer research has been very active because the good thing about cancer is, cancer cells proliferate so much, whatever they lack or have that is different from what a normal cell lacks or have, is amplified and gets easily noticed. It Is Normal to Stop Growing and Die Regulation of cell division is dependent on kinases, whose inactive forms are present at constant concentration in growing cells, and cyclins, which converts the kinases in their active form, and which has a fluctuating concentration. Once these cycline-dependent kinases are activated, they phosphorylate other proteins that affect particular steps in the cell cycle. Cell cycle has three points through which replication is regulated. Regulation occurs after the cells have grown in the G1 phase, where they either develop to its peak or divide further. Provided that mutations do not occur, if a cell goes beyond this point, it completes the cycle and produces two daughter cells. It is also regulated after they have completed preparations for cell division, and after mitosis. Regulation at these last two points helps ensure that, if mutation occurred in the preparation for mitosis, mutated cells do not enter mitosis and propagate further, and, if mutation occurred during the course of cell division, such as the chromatids not aligning properly in the metaphase plate, that resulting daughter cells do not end up with missing or extra chromosomes (Campbell and Reece, pp. 217, 226-227). Probably the most important protein that ensures regulated cell division is p53. DNA mutation activates p53 expression. In turn, p53 protein activates expression of other genes, such as p21, whose protein stops cell cycle momentarily by binding to cyclin-dependent kinases, to buy time for DNA repair machinery that is also activated by p53 protein. Once the extent of mutation proves to be unmatched against the repair mechanism, the p53 protein activates apoptosis (Campbell and Reece, pp. 371). Programmed cell death, called apoptosis, is a vital attribute of the cell cycle. If a cell divides unchecked, and something went wrong beyond repair, apoptosis will occur to immediately eliminate what would otherwise turn into cancerous cells. If the cells are destined to undergo cell death for the development of the organism, apoptosis must occur. For humans, about 1011 cells in an adult die each day and are replaced by other cells. The process may seem not to promote life, but it is one of the reasons why life in general is still existent. The body, a composite of somatic cells, is, in essence, destined for one purpose only, to ensure that the germ cells, the oocytes and the spermatocytes, come to their full term, join germ cells of a different genetic make-up but of the same species, and produce a progeny. It is the only means by which copies of their genes are propagated (Gilbert, p. 143). When Escaping Death Is Not Good The nucleus is the control centre of every cell. It contains genetic material that give a cell all its instructions, including when to divide, when to differentiate, and when to die. This genetic material is written as a chain of nucleotides, which is known as deoxyribonucleic acid or DNA. A species’ genetic material is an organization of genes that are efficiently arranged in the nucleus as chromosomes. Human genes are contained in 23 chromosomes that are passed down from one generation to the next. The instruction for each gene is usually to make a specific protein that controls various aspects of cell function. Some genes can be turned on to activate specific functions and others turned off. This is what differentiates one cell from another and allows cells to perform specific tasks. It is imaginable how an aberration can have monumental effects on cell physiology. Cellular pathway or pathways will either be truncated, and or will take a different route. Mutations are gene defects. When the DNA sequence of a gene is altered, through deletion, insertion, or replacement of one or more nucleotides, various consequences could happen. Mutations can be hereditary or acquired. Hereditary mutations are passed down from parents to offspring so that some people are simply born with mutations. However, one may be born with a mutation, but it does not necessarily mean that it was inherited from the parents. There are numerous cases wherein mutations may occur. It may have resulted from aberrations during the production of sex cells, or in mitosis during early stages of fertilized egg to a fetus. These acquired mutations may be caused by some external factor such as radiation or toxins, which are then called teratogens. Mutations occur in our bodies at all times, no matter how efficient our DNA replication machinery is, because efficient does not mean perfect. Even without mutagens, DNA aberration still occurs. But in most instances, when they occur, an instruction is given to the cell to fix it. For advanced organisms such as humans, for example, a part of their DNA polymerase goes back to the newly replicated chain of nucleotides, checks if there are any miscues, and fixes immediately the mutation, if present. Even then, more than 10-6 mutations per gene per cell division occur. Another one of dealing with cells containing mutated DNA is through apoptosis. Cancer occurs when a cell with DNA mutation does not die, because the mutation is not repaired, and the cell cannot undergo programmed cell death because the mutation influences apoptosis and cell division. How Good Genes Turn Bad Based on what was mentioned about the proteins that regulate cell division, differentiation, and apoptosis (i.e., kinases and cyclins), and about how imminent and consequential DNA mutation is, in despite of repair mechanisms, it is not surprising that there are several genes that, when mutated, can be cancerous. Indeed, cancer research has identified three major classes of cancer-prone genes. Oncogenes are mutations of good genes called proto-oncogenes. Proto-oncogenes, or proliferation genes, tell a cell when to divide and how often. They induce expression of proteins that control proliferation or apoptosis. They are a part of human’s genetic make-up because cells normally multiply after a wound or tissue damage. When a proto-oncogene is mutated into an oncogene, the protein expressed by the proto-oncogene will be overly-expressed or hyperactive, and mutated cells will not stop multiplying. One of the well-studied proto-oncogenes is myc. C-myc specializes on making metabolism and protein synthesis efficient despite of depriving conditions. Efficient energy generators are needed for highly proliferating cells such as cancer cells. Not only does it promote expression of pro-proliferation proteins, it also inhibits antiproliferation protein expression such as that of p21. In addition, the hypoxic environment c-myc permits allow HIF, another transcription factor, to regulate glycolytic pathway and activate stem cell factor, further promoting tumor growth (Gordan, Thompson, and Simon, 2007, pp. 108-113). Tumor suppressor genes, or antiproliferation genes, are one class of good genes that signal a cell to stop multiplying or tell a cell to die. If one of these genes is damaged, there is no signal to tell the cell to stop multiplying, resulting to unhampered cell division. One of these genes is Retinoblastoma (Rb). This gene is worth mentioning because once unaltered, p53-mediated chemotherapy induces a cytotoxic response (Derenzini, et al., 2009, pp. 373-382). DNA repair genes, which fix damaged nucleotides in a DNA sequence, are also good genes. If these genes are damaged or not present, there is far greater likelihood of a cell’s damaged genes causing unchecked multiplication (Alberts, et al., 2007, p. 1663). There is another major difference between proto-oncogenes and tumor suppression genes that is not mentioned above. For diploid cells such as human cells, there are two alleles per gene. For dominant alleles, presence of one copy is enough for the cells to manifest its character. For recessive alleles, however, both heterologous chromosomes should bear a recessive type, so the cell manifests the phenotype the recessive character codes for. The phenotype of mutants of tumor suppression genes is recessive. Therefore, the tumor suppression gene needs to be mutated at two instances, one for each heterologue, for antiproliferation activity to cease. On the other hand, the phenotype of oncogenes is dominant. Thus, mutation at oncogene in only one of the heterologues will result to overproduction of mitosis promoters. The Verified Hypothesis for Future Use Most types of cancers form a mass, a tumor or neoplasm, but some, like leukemia, do not. When cancerous cells begin to spread or metastasize, they lodge in other parts of the body, creating more tumors. When it remains in the area where it originated, it is benign. Being benign or malignant of a cancer cell mass is one of the main factors considered in determining the best option for treatment available at present. But what if, instead of stopping cancer well after it has grown into a noticeable mass, we cure it before the mass even starts? We already know where cancer starts, that it is merely a genetic disease, so why don’t we stop its onset, instead of stopping its proliferation? Indeed these same questions are being asked by researchers embarking in current cancer researches. DNA vaccines are currently at the forefront of promising new cancer treatment. The idea is to make cancer cells be identified by the body’s immune system as the body. For example, Hung et al. (2007, pp. 127-135), after determining that mesothelin is overexpressed among the majority of ovarian cancer cell lines, concocted a potential DNA vaccine which includes mesothelin peptide and single chain trimers of HLA-A2 as potency enhancers, and successfully shown that this mix produced strong human-mesothelin peptide-specific immune response in HLA-A2 transgenic mice. Not only was it effective, it was also able to confer immunity against ovarian cancer cell lines other than HLA-A2. Protein therapy is also a good idea. The theory is, the proteins lacking in cancer cells but needed for normal cell physiology would be identified, and then those proteins will be delivered unto the cancer cells, making them normal again. However, until recombinant protein production can be done upscale much more easily, and a better drug delivery system is discovered. Protein therapy will remain a theory left untested. Concluding Remarks Cancer is a traitor illness. It drains the nutrients the body takes for a clump of useless cells. It eats up space that is originally meant for more functional structures. The most frustrating part is, the body cannot bring the immune system to act against cancer cells because these abnormally propagating cells are still acknowledged as cells that has the same genetic material as the normal cells. Cells of the essentially the same kind kill each other, and work, inadvertently, toward the destruction of the organism. The most fundamental difference between a normal cell and a cancer cell is that cancer cells do not mature, do not age, and do not undergo cell death like normal cells do. Cancer cells propagate abnormally because of irreversible mutations targeted at genes which produce proteins that are vital to cell differentiation and apoptosis, two of the most important cell functions. Specifically, mutations in proto-oncogenes, tumor suppressor genes, and DNA repair genes are cancerous. Since we are already able to identify where cancer originates, the next step should be looking for treatments that will stop cancer cells early in their proliferation. Initial successes in DNA vaccines prove to be promising, and new methods such as protein therapy can also be explored. Cited Works Alberts, B, Johnson, A, Lewis, J, Raff, M, Roberts, K, and Walter, P 2007, Molecular Biology of the Cell. Fifth edition. Garland Science: New York. Campbell, NA and Reece, JB 2002, Biology, Fourth edition, Benjamin Cummings, San Francisco. Derenzini, M, Brighenti, E, Donati, G, Vici, M, Ceccarelli, C, Santini, D, Taffurelli, M, Montanaro, L, and Trere, D 2009, “The p53-mediated sensitivity of cancer cells to chemotherapeutic agents is conditioned by the status of the retinoblastoma protein”, Journal of Pathology, vol. 219, pp. 373-382. Gilbert, SF 2003, Developmental Biology, Sixth edition, Sinauer, Massachusetts. Gordan, JD, Thompson, CB, and Simon, CM 2007, “HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation”, Cancer Cell, vol. 12, pp. 108-113. Hung, CF, Calizo, R, Tsai, YC, He, L, and WU, TC 2007, “A DNA vaccine encoding a single-chain trimer of HLA-A2 linked to human mesothelin peptide generates anti-tumor effects against human mesothelin-expressing tumors”, Vaccine, vol. 25, pp. 127-135. Read More