Mechanisms of Chemoresistance in Breast Cancer Cells
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2006
- Accession Number
- ADA456928
Entities
People
- Valerie Gouaze