Analysis of the Apoptotic Signal Transduction Cascade and New Differentially Expressed Genes in Drug Resistant and Sensitive Hematopoetic Cell Lines

Abstract

The development of a therapy-induced drug resistance is still one of the most important therapeutic limitations, but the mechanisms involved are largely unknown. In order to study supposed common steps in the development of a resistance against cytotoxic drugs with a quite different mode of action, we established drug resistant (doxorubicin, methotrexate, cisplatinum, vincristine) derivatives of six hematopoetic cell lines (Jurkat, U937, HL60, DoHH-2, K562, ARH77). Gene expression of drug resistant and the respective sensitive parental cell lines was analysed by suppressive subtractive hybridization (SSH). Differential expression of cDNA fragments was confirmed by Northern Blot analysis. As a result of this screening, the following genes showed a higher (at least 2-fold) or exclusive expression in the drug resistant variants: hsp90, serglycin, sorcin, BMPG (bone marrow proteoglycan gene) and PTI-1 (prostate-tumor-inducing gene 1).