Naslov
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

Autori
Brozović, Anamaria ; Fritz, Gerhard ; Zisowsky, Jochan ; Jaehde, Ulrich ; Osmak, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
2. Znanstveni simpozij sa međunarodnim sudjelovanjem 45. godina molekularne biologije u Hrvatskoj 50 godina dvostruke uzvojnice Knjiga sažetaka / Ambriović Ristov , Andreja ; Brozović, Anamaria - Zagreb : Institut Ruđer Bošković, 2003

Skup
2. Znanstveni simpozij sa međunarodnim sudjelovanjem 45. godina molekularne biologije u Hrvatskoj 50 godina dvostruke uzvojnice

Mjesto i datum
Zagreb, Hrvatska, 20.11.2003. - 21.11.2003

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
MAP kinases; tumor cells; DNA damage; cisplatin-resistance

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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