|
|
Charakterizace vlivu senescence na indukci a regulaci smrti nádorových buněk
Nováková, Gita ; Anděra, Ladislav (advisor) ; Truksa, Jaroslav (referee)
4 Abstract Senescence is a specific cell state distinquished by cessation of cell division and proliferation and changes in gene expression. Normal cells enter senescence after distinct number of cell divisions or in case of an unrepairable damage. Senescence in cancer cells can be induced by subliminal stress as sublethal treatment with certain drugs. Senescent cancer cells persist in the tissue and may secrete a number of factors and nutrients affecting surrounding cells. Senescence can thus change the response of cancer cells to various apoptogens during cancer therapy. In this study, we focused on the elucidation of presumed differences between normal proliferating and senescent cancer cells in their response to selected apoptogens. Implementing bromodeoxyuridine (BrdU)-mediated replication stress in cancer cells derived from pancreatic (PANC-1) or mesothelioma (H28) tumors, we efficiently forced these cells to acquire senescent phenotype. We document that these senescent cells gain higher resistance to combined TRAIL and homoharringtonine (HHT) treatment and enhance sensitivity to other apoptogens such as FasL, camptothecin and mVES. These cells also showed increased expression of anti-apoptotic protein c-FLIP in senescent cells and changes in the expression of some Bcl-2 family proteins....
|
|
|
Role of cFLIP/CFLAR protein in the activation and regulation of cell death
Ksandrová, Marie ; Anděra, Ladislav (advisor) ; Macůrková, Marie (referee)
Programmed cell death as a natural mechanism plays essential role in development and homeostasis maintenance through removal of damaged, unwanted or dangerous cells. The cell death is an irreversible proces must be strictly regulated and thus defects in the regulation of cell death could lead to serious/fatal diseases. There are also one of the reasons why cell death regulating mechanisms are subjects of intense research nowadays. c-FLIP is one of several important cell death regulators. Three distinct isoforms of c-FLIP were detected on the protein level in human organism (long c-FLIPL and two shorter variants c-FLIPS and c-FLIPR) that interact their main cellular partner procaspase 8. The functional consequences of their interaction (enhancement or suppression of procaspase 8 selfprocessing) depend on the cellular level of c-FLIP, expressed splice variants and extracellular signaling. As c-FLIP is an important component of cell death signaling pathways (apoptosis and regulated necrosis), its expression and functional posttranslational modifications are strictly regulated by several mechanisms. Upregulation of c-FLIP levels has been found in various types of tumor cells that are often resistant to anticancer treatment.
|
|
|
Charakterizace vlivu senescence na indukci a regulaci smrti nádorových buněk
Nováková, Gita ; Anděra, Ladislav (advisor) ; Truksa, Jaroslav (referee)
4 Abstract Senescence is a specific cell state distinquished by cessation of cell division and proliferation and changes in gene expression. Normal cells enter senescence after distinct number of cell divisions or in case of an unrepairable damage. Senescence in cancer cells can be induced by subliminal stress as sublethal treatment with certain drugs. Senescent cancer cells persist in the tissue and may secrete a number of factors and nutrients affecting surrounding cells. Senescence can thus change the response of cancer cells to various apoptogens during cancer therapy. In this study, we focused on the elucidation of presumed differences between normal proliferating and senescent cancer cells in their response to selected apoptogens. Implementing bromodeoxyuridine (BrdU)-mediated replication stress in cancer cells derived from pancreatic (PANC-1) or mesothelioma (H28) tumors, we efficiently forced these cells to acquire senescent phenotype. We document that these senescent cells gain higher resistance to combined TRAIL and homoharringtonine (HHT) treatment and enhance sensitivity to other apoptogens such as FasL, camptothecin and mVES. These cells also showed increased expression of anti-apoptotic protein c-FLIP in senescent cells and changes in the expression of some Bcl-2 family proteins....
|
guest ::
