Electronic Journal of Polish Agricultural Universities (EJPAU) founded by all Polish Agriculture Universities presents original papers and review articles relevant to all aspects of agricultural sciences. It is target for persons working both in science and industry,regulatory agencies or teaching in agricultural sector. Covered by IFIS Publishing (Food Science and Technology Abstracts), ELSEVIER Science - Food Science and Technology Program, CAS USA (Chemical Abstracts), CABI Publishing UK and ALPSP (Association of Learned and Professional Society Publisher - full membership). Presented in the Master List of Thomson ISI.
Volume 13
Issue 3
Veterinary Medicine
Wojciechowski M. , Wałkuska G. 2010. GENE 53P AND ITS ROLE IN TUMOR DISEASE, EJPAU 13(3), #14.
Available Online: http://www.ejpau.media.pl/volume13/issue3/art-14.html


Monika Wojciechowski, Grażyna Wałkuska
Subdepartment of Toxicology and Environmental Protection, Department of Pre-clinical Veterinary Scence, University of Life Sciences, Lublin, Poland



The study comprised an analysis of dimensional changes in thin wood-based boards caused by cyclical changes in relative humidity at constant ambient temperature. Analyses were conducted on MDF, HDF, PB and OSB. As a result of these investigations it was found that final relative dimensional changes are significantly dependent on changes in dimensions occurring at individual stages of conditioning, with the first adsorption changes being most important. The lowest relative change in length determined in relation to the initial length was found for MDF board, while that in thickness – for HDF board.

Key words: p53 gene, tumor disease, chemotherapy.


Tumor's appearance and growth is a multiphase process. The main phenomenon are the inherited or acquired mutations of genes responsible for the growth and control of cell proliferation.  They are proto-oncogenes and tumor supressor genes (anti-oncogenes). An initiation of malicious transformation of a normal cell into a tumor one occurs as a result of the change of proto-oncogenes into oncogenes or loss of function by the tumor suppressor genes [34,39].


The main representative of the latter is the p53 gene which encodes the p53 protein, first identified in 1979 as cell protein binding the T antigen of the simian virus 40 [29,35]. Originally it was assumed that p53 is an oncogene, as its expression was found out in tumor cells. Further research, however, proved that this expression involved an incorrect, mutated p53 gene [78]. The correct (wild) type of p53 oncogene inhibits tumor transformation, so it is a suppressor gene of oncogenesis [15]. This was confirmed by the research on the Li-Fraumeni syndrome in people, the genetic disease often accompanied by the p53 gene mutation [41]. People with this syndrome usually develop malicious tumors e.g. breast tumour, sarcoma or others.  The laboratory tests proved that mice with removed p53 gene can develop normally but, relatively to the control group,  they develop a higher risk of malicious tumor occurrence and they usually die between the 3rd -6th month [14,36]. In the last years the p53 gene has been given numerous nicks like 'the guardian of the genome'[30, 'the good and bad cop' [61], 'the acrobat of tumorigenesis' [47], 'the death star' [75]. In 1993 the magazine 'Science' declared the p53 gene 'the particle of the year' [20]. The title was fully deserved, as today the product of the wild-type p53 gene is considered to be one of the essential proteins inhibiting cancer development [3,8,18]. However, the role of the wild-type p53 gene in chemotherapy is controversial as the latest research has proved that it can stop tumor cells in the cell cycle, protecting them from the cytostatic drugs. [4,5,6].


In normal cells the gene is not active and, to use a clever comparison from the 'Nature' magazine, analogous to electronic equipment, it stays at 'standby' and its amount is maintained at a low level [73]. The gene is activated and the amount of the p53 protein grows rapidly in response to particular factors causing cell stress such as e.g. hypoxia, activation of oncogenes, excessive cell proliferation or DNA damage caused by radiation, carcinogenes, cytotoxic drugs [54,56,73,74]. It has long been known that the p53 protein's expression inhibits the growth of a damaged cell by keeping it in phase G1 of the cell cycle, i.e. at the stage when it is still possible to repair DNA so that the error is not copied (Madej ksiazka). If the damage is irreversible then the cell is directed towards apoptosis. That is why the damaged DNA matrix is not replicated and the genetic anomalies do not occur in the daughter cells [9,21,46,55].

Gene p53 is a transcriptional factor triggering the transcription of a range of genes, including, among others, GADD 45, p21 waf1/cip1 genes responsible for stopping the cell cycle, Bax, Apaf 1, PUMA, NOXA genes stimulating apoptosis, maspin and KAI1 genes inhibiting angiogenesis [18,63]. Protooncogenes bcl-2 and c-myc also belong to the group of genes whose oncogenesis is inhibited by p53 [8,44]. Failure to inhibit their expression can lead to uncontrolled cell growth and cause an occurrence of cancer [32,45]. The gene family bcl-2 includes pro- and anti-apoptopic proteins, whose mutual interdependence ensures cell homeostasis. A normal, not mutated protooncogene bcl-2 is an indispensable factor necesarry, for instance, for the survival of mature lymphocytes T and B [58,62,70]. Failure to inhibit the bcl-2 gene's expression by p53 gene (as a result of its inactivation or mutation) can cause overexpression of bcl-2 gene and impairment of apoptopic answer resulting from DNA damage. It was proved that overexpression of bcl-2 gene can cause cancer disease not by the stimulation of abnormal cells' division but by the inhibition of apoptosis [66]. Another gene essential for carcinogenesis gene is protooncogene c-myc [13]. It was proved that overexpression of this gene is correlated with cancer transformation of cells in numerous organs [17]. Protooncogene c-myc takes part in the processes of growth and differentiation of normal cells and is active in the growing cells [67].  Overexpression of the c-myc gene, possible after the loss of inhibition by p53, stimulates the progresssion of the cell cycle [2,8].

As  the p53 gene is a strong  cell growth inhibitor, its activity must be strictly controlled. This is done by the  mdm2 protein, which inhibits the transcription activity of p53 and  stimulates its degradation [55]. The main function of  mdm2 is maintaining p53 at a very low level in physiological conditions. Mdm2 and p53 co-operate on the feedback basis [11,43,76]. The role of mdm2 gene in the  control of p53 activity was proved in the test in which mice embryos deprived of mdm2 gene died soon after implantation [24,48]. The hypothesis was then put forward that the embryos' death resulted from the uncontrolled activity of  p53 gene in early  embryogenesis. These observations were then confirmed by other laboratory investigations, in which mice deprived of both the mdm2 and p53 genes were able to survive [24,25,48]. Amplification of mdm2 gene is one of the mechanisms inactivating  p53 gene, which lead to cancer development. Amplification of mdm2 gene was proved in cases of human sarcoma containing the wild-type (i.e. normal, not mutated) p53 gene [9].


The most frequent p53 inactivating mechanism are point mutations, deletions and insertions found out in 50-80% of tumor disease cases in humans, e.g. in the breast, bone, colon or lung cancer [1,8,9,18,21,26,52,59,72,78]. It is suspected that  p53 is the most frequently mutated gene in human cancers [78]. In animals the p53 gene also plays a significant role in carcinogenesis. The performed research has clearly proved that this gene is inactivated (mutated) in numerous cancer cases in dogs (cancers of thyroid, bone, periannal glands, mammary gland or lymphoma)   [10,16,22,23,26,57,64,69,71]. In the research carried out by Setoguchi et.al. [59] mutations of  p53 gene were found in 47% cancer cases in dogs (leukemia, lymphoma, osteosarcoma). Similarly as in humans, the most common here were point mutations, deletions and insertions. In mammary gland cancer in dogs the p53 gene's overexpression was proved in 20-75% of cases [19,31,49,72]. In the authors' own research the p53 gene's overexpression was proved in as many as  86 % cases of mammary gland cancer in bitches [68]. It was found out that the p53 genes also played an important role in the pathogenesis of enzootic leukemia in cattle and that they may be a factor influencing the selective proliferation of lymphocytes B [40].

The p53 gene may also be inactivated due to the activity of oncogenic viruses, e.g.  HPV (human papilloma virus), HBV (hepatitis B virus) or CMV (cytomegalovirus) [3, 8]. These viruses combine with the p53 protein and thus inhibit its  transcription activity [74].

The activity of p53 gene depends to a great extent on its place in the cell. The gene can function correctly only if it is placed in the cell's nucleus whereas in the cytoplasm it remains inactive [33,74]. The p53 gene's transport from the nucleus to  cytoplasm and from the cytoplazm to nucleus is controlled by, among others, the  mdm2 gene [55].


The p53 gene's status (normal or mutated) is an important prognostic factor in cancer disease. It was found out in in vitro research that an introduction of p53 gene to the cancer cells which had not contained it before caused their prompt death or prevented their further division [42]. According to some authors the presence of mutations in p53 gene predicts bad prognosis, more aggressive course of the disease as well as a shorter life span and resistance to chemotherapy [1,18,21,37,38,53,64]. Exposition of cells to DNA-damaging factors, e.g. ionizing radiation or chemotherapy induces a high level of  the wild-type p53, which results in the DNA repair or apoptosis. After exposition to γ radiation or actinomycin D,  the cells of myeloid leukemia as well as the normal  cells of bone marrow containing the wild-type p53 stop their cell cycle simultaneously with an increase of p53 protein in the cell. However, those bone marrow cells which do not contain the wild-type p53 as well as those  with an overexpression of the mutated p53 do not stop their cell cycle after exposition to the damaging factors [27,28,77].  On the basis of the performed tests it was found out that the presence of the wild-type p53 can be an important factor affecting an organism's response  to anticancer therapy [8]. The latest discoveries, nevertheless, have shown that the role of the wild-type p53 in chemotherapy effectiveness is controversial, as it can stop the cancer cells in the cell cycle, protecting them from the action of cytostatic agents. Moreover, the mutated  p53 gene may fail to fulfill its function as the oncogenesis supressor and may start acting as the oncogene stimulating the carcinogenesis [8]. The in vivo observations showed a variety of the p53 gene's actions. Out of 80% breast cancer cases in women with the normal p53 gene, treated with  epirubicin and cyclofosfamid,  65 % cases did  not react to treatment, whereas in 60% out of 28 tumors with the mutated p53 the therapy was proved effective [4,5]. In response to the DNA damage caused by a chemotherapeutic agent, the wild-type p53 may either induce apoptosis and thus cause the tumor's regression or keep the cancer cells in the cell cycle, causing their resistance to chemotherapy. And the mutated  p53 may result in the piling of genetic faults and either lead to  further tumor's growth or cause its regression by an impairment of the mitosis process [6].

The p53 gene also plays a role in the prevention of teratogenic changes caused e.g. by ionizing radiation. Faults in the embryogenesis also frequently arise at the stage of blastula and gastrula as they are especially sensitive to disorders in the functioning of the p53 gene [12]. In pregnant mice with the normal p53 gene subjected to ionizing radiation 20% of anomalies were found as well as 60% of foetus deaths, whereas in mice without the p53 gene as many as  70% anomaly cases were found and only 7% of foetus deaths [51]. In experiments carried out by Nicol et.al. on pregnant mice with removed  p53 gene, subjected to the action of benzopyrene (a well known carcinogen), a four-times higher occurrence of teratogenic changes was found in foetuses relatively to the control group [50].


Knowledge of the interdependencies among genes and their influence on carcinogenesis is essential for an efficient gene therapy. This method is a fast-growing field of science and it will undoubtedly become a crucial element in the therapy of cancer disease.  It is a real hope for a more effective cancer treatment. It is possible that the further genetic research, within which the studies on the  p53 gene have a special importance, will allow to reduce cancer to a chronic, but controlled, disease.


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Accepted for print: 16.08.2010

Monika Wojciechowski
Subdepartment of Toxicology and Environmental Protection,
Department of Pre-clinical Veterinary Scence,
University of Life Sciences, Lublin, Poland
Akademicka 12, 20-033 Lublin, Poland
email: monika.wojciechowski@up.lublin.pl

Grażyna Wałkuska
Subdepartment of Toxicology and Environmental Protection,
Department of Pre-clinical Veterinary Scence,
University of Life Sciences, Lublin, Poland
Akademicka 12, 20-033 Lublin, Poland

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