Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression

Biochemical and Biophysical Research Communications

Volumn 391, Issue 1, 2010, Pages 219-223

  Erez Roman, Racheli ^a   Pienik, Reut ^a   Futerman, Anthony H ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Breast cancer; Ceramide; Real time PCR; Sphingolipid

Indexed keywords

CERAMIDE SYNTHASE 1; CERAMIDE SYNTHASE 2; CERAMIDE SYNTHASE 3; CERAMIDE SYNTHASE 4; CERAMIDE SYNTHASE 5; CERAMIDE SYNTHASE 6; ESTROGEN RECEPTOR; MESSENGER RNA; SPHINGOSINE ACYLTRANSFERASE; SPHINGOSINE KINASE 1; SPHINGOSINE KINASE 2; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; BREAST CANCER; CANCER TISSUE; CLINICAL ARTICLE; CONTROLLED STUDY; GENE EXPRESSION; HISTOLOGY; HUMAN; HUMAN CELL; INTRADUCTAL CARCINOMA; LYMPH NODE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR VOLUME; VASCULAR ENDOTHELIUM;

ADULT; AGED; AGED, 80 AND OVER; BREAST NEOPLASMS; CARCINOMA, DUCTAL; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MEMBRANE PROTEINS; MIDDLE AGED; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); RNA, MESSENGER; TUMOR SUPPRESSOR PROTEINS;

EID: 72949118520     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2009.11.035     Document Type: Article

References (28)

1. Ogretmen B., and Hannun Y.A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat. Rev. Cancer 4 (2004) 604-616
2. Zeidan Y.H., and Hannun Y.A. Translational aspects of sphingolipid metabolism. Trends Mol. Med. 13 (2007) 327-336
3. Senchenkov A., Litvak D.A., and Cabot M.C. Targeting ceramide metabolism - a strategy for overcoming drug resistance. J. Natl. Cancer Inst. 93 (2001) 347-357
4. Min J., Mesika A., Sivaguru M., Van Veldhoven P.P., Alexander H., Futerman A.H., and Alexander S. (Dihydro)ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1. Mol. Cancer Res. 5 (2007) 801-812
5. Reynolds C.P., Maurer B.J., and Kolesnick R.N. Ceramide synthesis and metabolism as a target for cancer therapy. Cancer Lett. 206 (2004) 169-180
6. Hannun Y.A., and Obeid L.M. The ceramide-centric universe of lipid-mediated cell regulation: Stress encounters of the lipid kind. J. Biol. Chem. 277 (2002) 25847-25850
7. Karahatay S., Thomas K., Koybasi S., Senkal C.E., Elojeimy S., Liu X., Bielawski J., Day T.A., Gillespie M.B., Sinha D., Norris J.S., Hannun Y.A., and Ogretmen B. Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC): attenuation of C(18)-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis. Cancer Lett. 256 (2007) 101-111
8. Koybasi S., Senkal C.E., Sundararaj K., Spassieva S., Bielawski J., Osta W., Day T.A., Jiang J.C., Jazwinski S.M., Hannun Y.A., Obeid L.M., and Ogretmen B. Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas. J. Biol. Chem. 279 (2004) 44311-44319
9. Senkal C.E., Ponnusamy S., Rossi M.J., Bialewski J., Sinha D., Jiang J.C., Jazwinski S.M., Hannun Y.A., and Ogretmen B. Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas. Mol. Cancer Ther. 6 (2007) 712-722
10. Futerman A.H., and Hannun Y.A. The complex life of simple sphingolipids. EMBO Rep. 5 (2004) 777-782
11. Pewzner-Jung Y., Ben-Dor S., and Futerman A.H. When do Lasses (longevity assurance genes) become CerS (ceramide synthases)? Insights into the regulation of ceramide synthesis. J. Biol. Chem. 281 (2006) 25001-25005
12. Lahiri S., and Futerman A.H. LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor. J. Biol. Chem. 280 (2005) 33735-33738
13. Riebeling C., Allegood J.C., Wang E., Merrill Jr. A.H., and Futerman A.H. Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J. Biol. Chem. 278 (2003) 43452-43459
14. Venkataraman K., Riebeling C., Bodennec J., Riezman H., Allegood J.C., Sullards M.C., Merrill Jr. A.H., and Futerman A.H. Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. J. Biol. Chem. 277 (2002) 35642-35649
15. Laviad E.L., Albee L., Pankova-Kholmyansky I., Epstein S., Park H., Merrill Jr. A.H., and Futerman A.H. Characterization of ceramide synthase 2: Tissue distribution, substrate specificity and inhibition by sphingosine 1-phosphate. J. Biol. Chem. 283 (2008) 5677-5684
16. Mizutani Y., Kihara A., and Igarashi Y. LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity. Biochem. J. 398 (2006) 531-538
17. Spiegel S., and Milstien S. Sphingosine-1-phosphate: An enigmatic signalling lipid. Nat. Rev. Mol. Cell Biol. 4 (2003) 397-407
18. Schiffmann S., Sandner J., Birod K., Wobst I., Angioni C., Ruckhaberle E., Kaufmann M., Ackermann H., Lotsch J., Schmidt H., Geisslinger G., and Grosch S. Ceramide synthases and ceramide levels are increased in breast cancer tissue. Carcinogenesis 30 (2009) 745-752
19. Mizutani Y., Kihara A., and Igarashi Y. Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem. J. 390 (2005) 263-271
20. Pyne S., Lee S.C., Long J., and Pyne N.J. Role of sphingosine kinases and lipid phosphate phosphatases in regulating spatial sphingosine 1-phosphate signalling in health and disease. Cell Signal. 21 (2009) 14-21
21. Saddoughi S.A., Song P., and Ogretmen B. Roles of bioactive sphingolipids in cancer biology and therapeutics. Subcell Biochem. 49 (2008) 413-440
22. Vadas M., Xia P., McCaughan G., and Gamble J. The role of sphingosine kinase 1 in cancer: oncogene or non-oncogene addiction?. Biochim. Biophys. Acta 1781 (2008) 442-447
23. Marchesini N., and Hannun Y.A. Acid and neutral sphingomyelinases: Roles and mechanisms of regulation. Biochem. Cell Biol. 82 (2004) 27-44
24. Ruckhaberle E., Rody A., Engels K., Gaetje R., von Minckwitz G., Schiffmann S., Grosch S., Geisslinger G., Holtrich U., Karn T., and Kaufmann M. Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res. Treat. 112 (2008) 41-52
25. Ruckhaberle E., Karn T., Rody A., Hanker L., Gatje R., Metzler D., Holtrich U., and Kaufmann M. Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer. J. Cancer Res. Clin. Oncol. 135 (2009) 1005-1013
26. Krishnamurthy K., Wang G., Rokhfeld D., and Bieberich E. Deoxycholate promotes survival of breast cancer cells by reducing the level of pro-apoptotic ceramide. Breast Cancer Res. 10 (2008) R106
27. Tran M.A., Smith C.D., Kester M., and Robertson G.P. Combining nanoliposomal ceramide with sorafenib synergistically inhibits melanoma and breast cancer cell survival to decrease tumor development. Clin. Cancer Res. 14 (2008) 3571-3581
28. Heakal Y., and Kester M. Nanoliposomal short-chain ceramide inhibits agonist-dependent translocation of neurotensin receptor 1 to structured membrane microdomains in breast cancer cells. Mol. Cancer Res. 7 (2009) 724-734