CYTOKERATIN EXPRESSION RESULTS IN A DRUG-RESISTANT PHENOTYPE TO 6 DIFFERENT CHEMOTHERAPEUTIC-AGENTS

The cytokeratin network is an abundant cytoplasmic system whose functi on is largely unknown, Recently, we have found that the introduction o f a cytokeratin network into eukaryotic cells results in a drug resist ance phenotype, The current study was undertaken to determine the univ ersal nature of this phenomenon by investigating the survival response of two different cell lines to six different DNA-damaging agents usin g two different assays of cell survival, To correlate our in vitro ass ays of survival with known in vivo responses to DNA damage, we compare d the apoptotic response of cytokeratin-positive and cytokeratin-negat ive cell lines, The results show that the introduction of a cytoskelet al network confers a resistant phenotype to mitoxantrone, doxorubicin, melphalan, bleomycin, and mitomycin C in the different cytokeratin-po sitive cell lines, No survival advantage was noted when damage was con ferred by cisplatin or UV irradiation, We found the cytokeratin-positi ve cell lines were protected from apoptosis, while the cell lines with out cytokeratins showed apoptosis in response to mitoxantrone exposure , Cytokeratin-dependent drug resistance is observed in different cell lines but is not observed with all DNA-damaging agents, The data sugge st that the mechanism of this drug resistance may be attributed, in pa rt, to a cytokeratin-conferred protection against apoptosis.