Kategorie: Maligní lymfomy a leukémie
Téma: Keynote lectures of invited speakers
Číslo abstraktu: 010
Autoři: Dr. Castiel Asher, M.Sc.
We have previously shown that SIL is over expressed in multiple types of cancers and its expression correlates with the expression of mitotic checkpoint genes. To understand the role of SIL in cancer, we have constructed an inducible RNAi system targeting SIL in colon cancer cell line. Knockdown of SIL blocks mitotic entry and causes apoptosis of these colon cancer cells in vitro and in vivo. The SIL knockdown related death phenotype was also observed in a variety of cancer cells representing the most common types of human cancer (cervical, lung, breast, prostate, gliomas and renal cancer) using anti-SIL siRNA oligonucleotides. This lethal phenotype can be rescued by the murine SIL, showing specificity of the siRNA effect. SIL is not necessary, however, for survival of normal proliferating cells as there are mouse embryonic stem cells and fibroblasts that are negative for the SIL gene.
SIL seems to be a novel regulator of mitotic entry, and thus crucial for the survival of cancer cells. Since cancer cells are extremely sensitive to anti-mitotic drugs, much effort is being invested in the development of drugs targeting mitotic regulators. Thus, targeting SIL (by either our shRNA or specific small inhibitors) may be a novel anti-cancer therapy. Since SIL may be a part of a novel mitotic and survival pathway, the combination of anti-SIL therapy with exiting mitotic drugs may improve anti-cancer treatment efficacy.
Datum přednesení příspěvku: 24. 4. 2009