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

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 0.1-10.0µM) 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.k e y w o r d s: Breast cancer, chemoresistance, adaptor proteins, Ruk/cIN85.