Abstract
Purpose: Multidrug resistance (MDR) has been linked to sphingolipid metabolism and preclinical data ascribe glucosylceramide synthase (GCS) a major role for MDR especially in breast cancer cells but no profound data are available on the expression of this potential therapeutic target in clinical breast cancer specimens. Methods: We analyzed microarray data of GCS expression in a large cohort of 1,681 breast tumors. Results: Expression of GCS was associated with a positive estrogen receptor (ER) status, lower histological grading, low Ki67 levels and ErbB2 negativity (P < 0.001 for all). In univariate analysis there was a benefit for disease free survival for patients with tumors displaying low levels of GCS expression but this significance was lost in multivariate Cox regression. Conclusions: Our results suggest ER positive tumors may be the most promising candidates for a potential therapeutic application of GCS inhibitors.
| Original language | English |
|---|---|
| Journal | Journal of Cancer Research and Clinical Oncology |
| Volume | 135 |
| Issue number | 1 |
| Pages (from-to) | 81-90 |
| Number of pages | 10 |
| ISSN | 0171-5216 |
| DOIs | |
| Publication status | Published - 01.2009 |
Funding
Acknowledgments We thank Samira Adel and Katherina Kourtis for expert technical assistance. This work was supported by grants from the Deutsche Krebshilfe, the Margarete Bonifer-Stiftung, Bad Soden, the Dr. Robert PXeger-Stiftung, Bamberg, and the BANSS-Stiftung, Biedenkopf.
