The precise presentation of mechani­sms, that decide about activity of cell will help to understand, why only non-numerous suffer from the cancer, even though in organism of every human many mutated cells is daily formed.

Before healthy cell divides, many metabolic changes preparing it to this process must take place. Successively following phases after each division have identical course and are closed in so called cellular cycle.

The cellular cycle (see: scheme on the page before) consists of phases marked with symbols G₁ S, G₂ and M. It depends on very complicated regulation, ensuring proper course of the whole process. On the border of each phase so called control points exist. If the cell’s state does not fulfil all required criteria, the cell cannot enter in the next phase of preparations.

In G₁ phase processes preparing the cell to double its genetic material take place. In S phase amount of DNA becomes doubled. In G₂ further preparation of cell to division is observed. In M phase the formed structures are divided into two progenitor cells.

In the control point localised between the G₁ and S phase, control of genetic material integration is made. Finding of DNA destruction causes stopping of cellular cycle and cell remains in suspension so long, until the activated repairing systems will not remove the destruction. In G₂/M control point control of genetic material segregation is made.

As a result of proper division from maternity cell, two identical sisterly progenitor cells, having quantitatively and qualitatively precisely the same genetic information are formed. Protein product (called p53) of suppressor gene TP53, which probably is of key importance in tumours development, plays very important role in control of correctness of the course of cellular circle. Biologically active molecule of p53 protein possesses the ability to bind with DNA and at the same activate some genes. For this reason TP53 is called “guard of genetic material". If during the division in DNA of cell dangerous destructions appear, number of functional p53 molecules in the cell increases. Increase of this protein content activates genes responsible for discontinuation of further divisions and DNA repair. If the repair is impossible, the protein activates the process of cellular self-destruction. That is why loss of gene TP53’s activity almost always is a phase leading to neoplastic transformation. TP53 protein is also a component necessary to product a factor stopping the process of neoangiogenesis. If in result of mutation level of this protein decreases, easier tumour’s progression can be observed.

Apoptosis - suicide for the reason

And what will happen, if destructions formed during the cycle are so serious, that cellular repair systems are not able to eliminate them? Then the cell is directed on path of programmed death (apoptosis), that is – speaking graphically – commits a suicide.

Process of apoptosis can be divided into two phases. In the first phase cell must decide about committing a suicide, with the help of information obtained from other cells as well as from the own interior. Internal signals concern the course of metabolic processes and processes connected with divisions. Environmental information is i.a. hormones reaching the cell together with blood or from adjacent cells. In the second phase of apoptosis “genes of death" become active, which protein products take part in cellular autodestruction. One of them is a gene called BCL2, which cooperates with gene MYC. Level of protein product of gene MYC decides, if cell is going to be directed on path of death or division. Whereas which of these paths will be chosen, decide other signals reaching the cell. If signals of survival prevail – cell starts to divide. If signals of death win – cell commits a suicide. Scientists suppose that exactly the product of gene BLC2 is one of the most important signals of survival, because its high activity favours a survival of cell, and its weakness is equivalent with directing the cell on path of apoptosis.

Proving a role of oncogenes in programmed death of cell, suggested a question about the role of suppressor genes in neoplastic transformation. It has been discovered, that product of suppressor gene TP53, whose destructions can be found in about 50% of tumours, takes part not only in regulation of cellular cycle, but also take a direct part in activation of genes starting the apoptosis.

The mistery of immortality

In each cell of human’s body, of diameter measured in thousand parts of millimetre, about two metres of DNA are found. How is it possible? DNA is winded up on proteins like thread on spool, creating finally the rod-shaped structures, called chromosomes. On end of each chromosome so called telomeres are located, that is repeating sequences of DNA, not coding any protein. They protect chromosomes against disintegration and prevent their coupling. Telomeres in each cell’s division become shorter. This is a kind of “biological clock" of cell. When after the next division the telomeres become critically short, cell dies from old age, entering the path of apoptosis.

In some healthy cells, i.e. stem cells, cells of germinal line and in some lymphocytes. In this way these cells may divide unlimited number of times. In case of these cells it is a normal phenomenon. Problem appears when telomerase activates in “unauthorised" cells. Exactly this mechanism (beside loss of ability to enter the apoptosis) is one of guarantors of immortality (more precisely: of not ageing) of tumour’s cells.

To deceive patrols

Accumulation of mutations alone is not enough for tumour’s formation. Rebellious cell must continuously deceive cells of the immune system that patrol the organism. If it does not succeed, it will be found and destroyed.

Each existing cell has on its surface a group of molecules, characteristic only and exclusively for itself and for organism in which it exists. Our immune system learns how to recognise and tolerate cells marked with own antigens, and eliminate cell with foreign antigens (bacteria, own cells infected with viruses). The same mechanism takes part in process of rejection of transplantation. Cells of transplanted organ, even in relative person, have different antigens. This is why cells of immune system treat them as the enemy. To avoid the rejection, people after transplantation are given drugs that suppress the immunity.

How the neoplastic cells can get out of control of the immune system? Part of cancer cells posses antigens present in organism, i.e. on germinal cells, which are not considered as a danger by the immune system (can be said, that cancer “pretends the embryo"). Antigens of neoplastic cells may have also such structure, which makes their recognition as foreign impossible. Some cancer cells can “hide" their markers under their surface. They can also cause a local immunosupression, which is a similar effect, as after administration of drugs suppressing the immune processes to person after transplantation. Tumours can also kill attacking cells of immune system, directing them on path of apoptosis.

After clash with immune system the neoplastic cells undergo after all some selection. These, which can be killed by immune system, die. Only the most resistant and dangerous, able to camouflage effectively remain. For this reason, although it seems that our immune system cannot the best cope with tumours, it should not be underestimated. In fact it controls on continuously our organism and deletes cells, which get out of its control.

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