Cytokeratin expression results in a drug-resistant phenotype to six different chemotherapeutic agents

John M. Anderson, Lisa M. Heindl, Patricia A. Bauman, Clint W. Ludi, William S. Dalton, Anne E. Cress

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The cytokeratin network is an abundant cytoplasmic system whose function is largely unknown. Recently, we have found that the introduction of a cytokeratin network into eukaryotic cells results in a drug resistance phenotype. The current study was undertaken to determine the universal nature of this phenomenon by investigating the survival response of two different cell lines to six different DNA-damaging agents using two different assays of cell survival. To correlate our in vitro assays of survival with known in vivo responses to DNA damage, we compared the apoptotic response of cytokeratin-positive and cytokeratin-negative cell lines. The results show that the introduction of a cytoskeletal network confers a resistant phenotype to mitoxantrone, doxorubicin, melphalan, bleomycin, and mitomycin C in the different cytokeratin-positive cell lines. No survival advantage was noted when damage was conferred by cisplatin or UV irradiation. We found the cytokeratin-positive cell lines were protected from apoptosis, while the cell lines without 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 suggest that the mechanism of this drug resistance may be attributed, in part, to a cytokeratin conferred protection against apoptosis.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalClinical Cancer Research
Volume2
Issue number1
StatePublished - Jan 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Cytokeratin expression results in a drug-resistant phenotype to six different chemotherapeutic agents'. Together they form a unique fingerprint.

Cite this