Tag Archives: breast cancer

Adaptor protein Ruk/CIN85 modulates resistance to doxorubicin of murine 4T1 breast cancer cells

I. R. Horak, D. S. Gerashchenko, L. B. Drobot

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

The acquisition of chemoresistance in the course of tumor progression includes activation of membrane ABC transporters, detoxification enzymes, cell cycle deceleration and activation of specific signaling pathways such as Akt/mTOR, MAPK, NF-κB. Adaptor proteins play an essential role in the assembly of supramolecular signaling complexes, maintaining and directing the intracellular signaling. One of such proteins, called Ruk/CIN85, is strongly associated with malignant transformation and metastasis. In present study we investigated the Ruk/CIN85 effect of up/down-regulation on the transforming potential and doxorubicin resistance of highly aggressive mouse breast adenocarcinoma 4T1 cells. It was demonstrated that 4T1 cells overexpressing Ruk/CIN85 possessed increased resistance to doxorubicin (in the range of concentrations 0.1–10.0 µM) while knockdown cells were the most sensitive. Also, high levels of Ruk/CIN85 in 4T1 cells positively correlated with their ability to form colonies in semi-solid agar. Ruk/CIN85-overexpressing cells formed four times more colonies in comparison with Ruk/CIN85 nockdown cells, the growth of which revealed higher resistance to doxorubicin action.

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.