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Cell dehydration Role in Cancer Risk

#A-1789


The Study of the Primary Role of Aging-Induced Cell Dehydration in the Increase of Cancer Risk

Tech Area / Field

  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • BIO-CHM/Biochemistry/Biotechnology
  • MED-DIS/Disease Surveillance/Medicine
  • MED-OTH/Other/Medicine

Status
3 Approved without Funding

Registration date
01.10.2009

Leading Institute
Life Sciences International Postgraduate Educational Center, Armenia, Yerevan

Supporting institutes

  • Scientific Technological Center of Organic and Pharmaceutical Chemistry, Armenia, Yerevan

Collaborators

  • Universidade de Lisboa / Instituto de Medicina Molecular, Portugal, Lisbon\nPolyclinique Maymard/Service de Cancerologie Medicale et de Radiotherapie, France, Bastia

Project summary

Cancer cells are characterized by overhydrated state. The increased cell hydration causes cancer not only by promoting cell pision and oncogene expression, but also by inactivating genes inducing cell differentiation and by preventing apoptosis. At the same time it is known that aging-induced tissue dehydration increases cancer risk. The dysfunction of the activity of Na+/K+ pump, which is one of the powerful metabolic regulators of cell hydration, is the common consequence of aging and carcinogenesis. This brings to the accumulation of intracellular Ca ions having malty poisoning effect on cell metabolism, including the feedback inactivation of Na+/K+ pump activity. The latter on the one hand increases the intracellular cAMP content, leading to the cell dehydration, and on the other hand it stimulates cell proliferation by Ca-induced activation of lipase activity. These data allow us to suggest that the aging-induced accumulation of intracellular Ca ions serves as a potential messenger for the initiation of cell carcinogenesis. By our early study it was shown that the intracellular cGMP has an activation effect on Ca ions extrusion from cell by Na+/Ca2+ exchange and Ca pump. Like other intracellular enzymes, the activity of guanylyl cyclase depends on its hydration (folding). Therefore, it is predicted that the aging-induced cell dehydration could inactivate its activity and depress cGMP formation and Ca extrusion from cell. Thus, the working hypothesis of the present project is whether the reason of the increase of cancer risk in aging is cell dehydration-induced weakening of cGMP-dependent Ca efflux from cell. To check this hypothesis a comparative study of cell hydration, electrogenic Na+/K+ pump and Na+/Ca2+ exchange activity, intracellular cAMP and cGMP, the number of functionally active 3H-ouabain receptors (Na+/K+ pump units) in cell membrane will be studied in normal thorax and carcinoma-180 tumor tissues in mice of different age and at different initial hydration of body tissues.

For this purpose isotope methods for studying ion transportation through membrane and counting the number of pump units (3H-ouabain receptors) in membrane, immunoassay methods for the measurement of intracellular cyclic nucleotides contents, light microscopy and impedance-metric methods will be used.


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