Search for novel proteins involved in the development of chemoresistance in colorectal cancer and fibrosarcoma cells in vitro using two-dimensional electrophoresis, mass spectrometry and microsequencing

In search of novel mechanisms that may lead to the development of chemoresi stance of malignant tumors of the large bower we used two-dimensional elect rophoresis to identify proteins that were overexpressed in colorectal and f ibrosarcoma cell lines that were resistant towards mitoxantrone. This cytos tatic drug is known to lead to atypical multidrug resistance, i.e., the cla ssical mechanism of multidrug resistance (MDR) accompanied by the overexpre ssion of P-glycoprotein (P-gp) is ineffective. Using mass spectrometry and microsequencing we found adenine phosphoribosyl transferase and breast canc er specific gene 1 (BCSG1) overexpressed in the resistant colorectal tumor cell line. In the chemoresistant fibrosarcoma cell line we found two protei ns that were overexpressed. One was identified as Rho-guanine dinucleotide phosphate (Rho-GDP) dissociation inhibitor and the other had sequence homol ogies with yeast protein yer-7. The putative role of these proteins is disc ussed.