Activation of SAPK/JNK, p38 kinase and AP-1 in human cervical carcinoma cells is related to DNA damage and involved in acquired resistance to cisplatin (CROSBI ID 495821)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Brozović, Anamaria ; Fritz, Gerhard ; Zisowsky, Jochan ; Jaehde, Ulrich ; Osmak, Maja
engleski
Activation of SAPK/JNK, p38 kinase and AP-1 in human cervical carcinoma cells is related to DNA damage and involved in acquired resistance to cisplatin
Human cervical carcinoma cells (HeLa) exposed to cisplatin (cDDP) acquired resistance to the drug. In a present study we analysed the underlying mechanism. We demonstrate that acquired resistance to cisplatin (ARC) is related to a lower frequency of cDDP-induced apoptosis. Analysis of apoptotic proteins revealed that, upon cDDP treatment, the levels of Fas L, Fas, Bax and Bid were unchanged whereas the levels of Bcl-2 and p-Bad were reduced in ARC cells, as compared to the parental cell line. cDDP provoked the induction of stress-activated protein kinase/c-Jun N-terminal protein kinase (SAPK/JNK) dose-dependently within 6 h upon treatment, with significantly lower level in ARC cells. Within the same time period, phosphorylation of p38 and c-Jun expression was enhanced and the activity of AP-1 was elevated. Again, this occurred to a lower extent in ARC cells. Regarding UV-C light, for which the differences in sensitivity were less obvious, both cell lines displayed similar activation levels of SAPK/JNK and p38. The data suggest that ARC is causally related to attenuated SAPK/JNK activation, leading to a lower level of expression of AP-1 and finally to a reduced apoptotic response. ARC cells displayed a lower overall DNA adduct level which indicates that cDDP-induced DNA damage is responsible for stimulation of SAPK/JNK, p38 kinase and c-Jun expression, leading finally to a decline of Bcl-2 and p-Bad and the induction of apoptosis.
MAP kinases; tumor cells; DNA damage; cisplatin-resistance
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Podaci o prilogu
41-x.
2003.
objavljeno
Podaci o matičnoj publikaciji
Ambriović Ristov , Andreja ; Brozović, Anamaria
Zagreb: Institut Ruđer Bošković
Podaci o skupu
2. Znanstveni simpozij sa međunarodnim sudjelovanjem 45. godina molekularne biologije u Hrvatskoj 50 godina dvostruke uzvojnice
poster
20.11.2003-21.11.2003
Zagreb, Hrvatska