Cancer Cell Biology the Fundamental Research Paper

Excerpt from Research Paper :

In the tissue culture, they usually proliferate indefinitely. The normal constraints which limit the growth of the cells absent in the cancerous state and are also characterized by the division ability for number of generations which is unlimited.

Cell cycle and cancer

With millions of chemical reactions taking place concurrently and in specific areas, the human body can be thought of as a small laboratory. It is the only "machine" with the ability to save fuel when fed in excess and also know to bring out the reserves when facing starvation, capable to protect itself from attacks by viruses and bacteria, ability to make adjustments to withstand changes of weather and the ability to learn, think and create on its own. The human body system is well integrated and organized, able to perform vital functions important to its survival. Malfunctions in the body can have damaging results that range in severity from discomfort to life threatening illnesses. Many processes and reactions taking place within the cells are tightly controlled, an example being cell division. Cell division involves a series of reactions and changes like DNA replication and protein synthesis involving cooperation between arrays of proteins to achieve a common goal.

Cell division is divided into four phases where normal cell division progresses from one phase to the next with strictly controlled "checkpoints." These serve as safety measures for the cell that prevent the control system from dictating the start of another cell cycle event before the previous one as finished or before any damage to the cell has been repaired accordingly. The cell division cycle also depends on external cues. In case cell division is unregulated, and is independent of the external cues, there is possibility of one developing cancer, one of the most devastating diseases in the world (Michor & Nowak, 2004, p.203).

Cell division cycle starts with the growth phase, followed by synthesis, second growth and mitotic phases. On receiving external cues, from growth factors released from neighboring cells, so as to initiate division, the cells move into the growth phase. Here, cells prepare for division by producing more proteins. DNA replication by the cells takes place in the synthesis phase. This brings about creation of identical copies to enable daughter cells inherit an exact copy of the DNA. In the second growth phase, synthesis of the proteins needed for the growth of the daughter cells takes place. The cell separates its DNA and divides into two in the mitotic phase.

Cell division requires the accurate replication and segregation of chromosomes. All the tasks are accomplished in an orderly manner if all the events related to cell division are coordinated throughout the cycle. An example is where cell division occurs before it attains its optimum size and as a result, smaller daughter cells result from the subsequent division. A set of interacting proteins forms the cell control system which is responsible for regulating the process of cell division. This system of proteins directs and coordinates other proteins that are involved in particular tasks like DNA replication. The control system still has to follow feedback signals from the cell cycle itself in spite of its ability to act on other proteins. There are other proteins in the cell cycle involved in surveillance control mechanisms. They are able to stop or delay the control systems' progress at the cycle checkpoints. The loss or inactivation of a gene encoding a protein in the surveillance system can result in susceptibility of developing cancer.

The cell cycle's control system is based on two families of proteins: namely the cyclins and cyclin-dependent kinases (CDK). The CDKs phosphorylate (add a phosphate group) key amino acid residues thus induce other proteins to perform their functions. Cyclins control the CDKs ability to phosphorylate by binding to the CDKs.

Many proteins involved in the surveillance system can delay or terminate the cell cycle progress. Some promote rapid degradation of cyclins and others prevent entry of CDK-cyclin complexes into the cell compartments where they are needed for cell cycle progression. The first checkpoint a cell encounters before entering a cycle is at transition between the dormant and growth phases. Retinoblastoma (Rb) gene is involved in encoding the protein involved in this stage which inhibits the passage of the cell past the cycle's starting point through shutting of transcription of genes necessary for cell division and
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sequestering the proteins involved in regulation of DNA replication. Rb gene importance is evident in the fact that many common types of cancers miss both its functional copies.

Once in the growth phase, the cell can continue unchecked until the beginning of the synthesis phase. The metaphase between the growth and synthesis phase ensures that DNA is intact before replication. p53, a protein, stops the progression of the cell cycle when even the smallest DNA damage occurs. It is produced in greater quantities when the cell is exposed to DNA-damaging agents like UV and radiation rays and also induces the synthesis of a protein that inhibits the CDK-cyclin complex. Li-Fraumeni syndrome is an indication of the lack of a good copy of the Rb gene, generally characterized by propensity to develop tumors in several tissues. This is due to the cell's increased chances of producing mutation-carrying daughter cells leading to formation of tumors since without the control of p53, the cell progresses from the growth to synthesis phase regardless of damaged DNA.

Other cell cycle checkpoints are found at the second growth and mitotic transition and the mitotic phase itself. In the second growth and mitotic phase checkpoint, a failure in complete DNA replication causes specific proteins to inhibit actions of the CDK-cyclin complex by preventing their entry into the nucleus. Within the mitotic phase, cell division is not made possible until the complete movement of chromosomes to opposite poles of the cell.

The large network of proteins involved in cell cycle progression and regulation means that we are unable to fully understand details it's functioning. Intense cancer research has uncovered many genes and their respective roles in the cell cycle. Through a gradual understanding of the mechanisms underlying the cell cycle, we can hopefully find the cure for cancer.

Cancer as a multistep Process

The idea which is principal contemporary molecular world is that the development of cancer is not instantaneous but it's a complex and long genetic changes succession happening across time. The acquisition of the some traits by the precancerous cells is enabled by the changes which then create a malignant cancer cells growth. The triggering of cancer role is played by two genes categories. The cell cycle is controlled by these genes in their normal forms. This is the events sequence by which the enlargement and division of the cells takes place. Cell division is encouraged by proto-oncogenes which is one of the categories of the genes. Tumor-suppressor gene which is the other category inhibits the cell division. The organs and tissue in the body is maintained to the structure and size which meets the needs of the body by regulation of the growth which is coordinated by both tumor-suppressor and proto-oncogenes genes.

It should then be noted that oncogenes then result from the mutation of the proto-oncogenes and they are responsible for the stimulation of excessive division. These genes are inactivated by the mutations in the tumor-suppressor genes therefore the cell division inhibition is eliminated which is critical in the normal excessive growth prevention. Most of the cell division which is not controlled in the human cancers is accounted for by the collective mutation of these genes (National Cancer Institute).

The role of oncogenes

Of importance is the role of the proto-oncogenes or more precisely the oncogenes that result from their mutations play in the cancer development. Signals involved in the growth stimulation are received and processed by molecular pathways that are coded by the proteins. A growth factor is first produced at the beginning of such signaling and this growth factor is basically a division stimulation protein. The specific receptor proteins which are found in the neighboring cell's surface is the place that the growth factor attaches to after moving through inter-cellular openings and spaces. A stimulatory signal is conveyed to the cytoplasm proteins by the receptor after a factor which is growth stimulating binds to it. Stimulatory signals are emitted by these proteins to other proteins in the cell till the nucleus of the cell receives the message promoting division and then a set of genes which aid the cell movement through its growth cycle is are activated (National Cancer Institute).

The growth promoting pathways protein is caused to be overactive by the oncogenes which is the mutated form of the proto-oncogenes. Therefore there is a faster proliferation of the cells than if the mutation had not occurred. The growth factors overproduction in the cells is caused by some oncogenes. The neighbor cells growth is stimulated by these factors but the excessive…

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