Suppressive subtractive hybridisation reveals differential expression of serglycin, sorcin, bone marrow proteoglycan and prostate-tumour-inducing gene I (PTI-1) in drug-resistant and sensitive tumour cell lines of haematopoetic origin.

摘要: The development of therapy-induced drug resistance is still one the most important therapeutic limitations. Nevertheless, an integrating view molecular mechanisms underlying in general missing. In order to shed some light on network this development, we established drug-resistant (doxorubicin (DX), methotrexate (MTX), cisplatin (cisPt), vincristine (Vin)) derivatives six tumour cell lines (Jurkat, U937, HL60, DoHH-2, K562 and ARH77) haematopoetic origin. Differential gene expression drug-sensitive parental thereof was analysed by suppressive subtractive hybridisation. After dot blot screening for differential sequencing cloned PCR fragments, confirmed Northern analysis. attempt discriminate differentially expressed genes only related or other investigated drugs, cDNAs various resistant sublines (doxorubicin-, methotrexate-, cisplatin-resistant Jurkat cells) were pooled compared with sensitive line. addition, different corresponding eliminate line variations that not resistance. As a result screening, following showed higher (at least 2-fold) exclusive variants: serglycin, sorcin, BMPG (bone marrow proteoglycan gene) PTI-1 (prostate-tumour-inducing 1). elevated hsp90, previously found our group be upregulated colon carcinoma LoVo H67P overexpressed HL60 cells.