Tag Archives: proliferation

Influence of human HB-EGF secreted form on cells with different EGFR and ErbB4 quantity

O. I. Krynina, N. V. Korotkevych, A. J. Labyntsev,
S. I. Romaniuk, D. V. Kolybo, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: olyakrynina@gmail.com

Received: 18 July 2019; Accepted: 13 August 2019

HB-EGF is one of the most potent ligands of EGFR and ErbB4 receptors. This growth factor plays a pivotal role in many cellular processes, but its effect differs from one cell type to another and remains not fully understood. The aim of this work was to investigate the dependence between the rate of HB-EGF mediated cell proliferation and activation of EGFR and ErbB4 receptors. Therefore, the effects of human recombinant sHB-EGF (rsHB-EGF) on the proliferation of cell lines with different EGFR and ErbB4 quantity and ratio, as well as activation of the MARK-cascade p38 and ERK1/2 (p42/44) kinases, were analyzed. For comparison, a similar study of the effect of native sHB-EGF secreted by human histiocytic lymphoma cells U937 during co-cultivation with different cell lines was performed.
It was proved that cell proliferation in response to sHB-EGF depends not only on the quantity but also on the ratio of EGFR and ErbB4. It was shown that signaling through ErbB4 is associated with activation of p38 kinase and signaling through EGFR associated with activation of ERK1/2 (p42/44) kinase. We assume the existence of two different mechanisms for sHB-EGF-mediated stimulation of cell proliferation, and the simultaneous launch of these mechanisms provides a maximal proliferative response. The results of this study support the feasibility of creating anti-proliferative drugs that target ErbB4.

Biological effects of thyroid hormones

T. S. Saatov, A. A. Abduavaliev

Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Tashkent;
e-mail: t.saatov@yandex.ru

The article presents the findings from the study on multifunctional effects of thyroid hormones in relation to normal and malignantly transformed tissues and cells. Both “rapid” and «slow» effects of thyroid hormones including calorigenic effects and effects over adenylate cyclase – cAMP system have been described.  Thyroxin (Т4) has been established capable to inhibit proliferation and to induce apoptosis of cells carrying Т4 receptors on their membranes as well as to change course of metabolic processes under its effect. Spectrum of Т4 targets is quite broad to include not only cells of hormone-producing organs, to name those of the breast and the colon, but also other types of cells to name melanin-containing ones; Т4 effects resulting in reconstruction of presentation of regulatory proteins on the cell membrane surface to ultimately activate the process of cell apoptosis.  Our findings help determine alternative paths for hormonal regulation of cell proliferation and apoptosis of cells of hormone-dependent tumors, breast cancer, in particular, upon impossibility to regulate the processes by conventional methods. This facilitates understanding mechanisms for activation of signal system of the breast cancer’s cells by hormones upon changes in expression of receptors on the cells’ surface, making possible development of novel strategy for replacement therapy of hormone-dependent tumors upon low efficacy of drug therapy.

Endoplasmic reticulum stress, its sensor and signalling systems and the role in regulation of gene expression at malignant tumor growth and hypoxia

O. H. Minchenko, A. P. Kharkova, T. V. Bakalets, I. V. Kryvdiuk

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com

Hypoxia is one of the inductors of the expression of a large group of genes, which control glycolysis and proliferation processes in low oxygen conditions or as a result of low oxygen consumption. Moreover, hypoxia is one of the factors which induce the endoplasmic reticulum stress which, like hypoxia, is an obligatory component of malignant tumor growth and is connected with cytoplasm and nuclei through three sensor and signalling systems: PERK, ATF6 та ERN1. The suppression of ERN1, the main sensing and signalling enzyme of endoplasmic reticulum stress, leads to a decrease of tumor growth and changes the character of hypoxic regulation of many genes responsible for the control of proliferation and glycolysis. ERN1 sensing­ and signalling system controls the expression of a large set of genes, which are dependent on endoplasmic reticulum stress as well as hypoxia. Moreover, this signalling pathway is an important factor of malignant tumor growth.