Mechanisms of Chemoresistance in Breast Cancer Cells
Annual rept. 1 May 2005-30 Apr 2006
JOHN WAYNE INST FOR CANCER TREATMENT AND RESEARCH SANTA MONICA CA
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The objective of this second year was to determine whether anticancer agents influence the expression of glucosylceramide synthase GCS. GCS is an enzyme which catalyzes ceramide glycosylation and is associated with chemotherapy resistance in cancer cells. Drugs like doxorubicin, cisplatin, etoposide, and taxol cells had no effect on glucosylceramide GC mass production in MCF-7 after short-term exposure 30 min-4 hr. After 24 hr, only taxol induced significant GC production. In short-term experiments using the full-length GCS promoter, C6-ceramide activated GCS after 4 hr treatment, whereas the chemotherapy drugs epirubicin, idarubicin, and doxorubicin enhanced GCS promoter activity at 48 hr. When MCF-7 cells were treated with ceramide generating drugs like etoposide, 4-HPR, doxorubicin, or cisplatin for 48 hr, GCS mRNA levels were unchanged compared to untreated cells. Moreover, C6-ceramide did not directly enhance GCS transcription.
- Medicine and Medical Research