These authors contributed equally in the present investigations.It has been shown that the p level is regulated by MDM and that various mutations of p are frequently detected in cancer cells.Although our knowledge of the events leading to chemoresistance is incomplete, failure to activate apoptosis in these cancer cells may confer resistance to these agents. An intensive search for modulators of apoptosis has revealed the presence of several potent endogenous suppressers in mammalian cells.The IAP family, originally identified in baculovirus, currently consists of five members: neuronal apoptosis inhibitory protein, human inhibitor of apoptosis protein, and survivin. Naip is believed to be involved in the pathogenesis of spinal muscular atrophy, in which apoptosis in the spinal ventral neurones is precipitated by the loss of this inhibitor and has been suggested to be an important etiological factor of carcinogenesis and potential new sites for apoptosisbased therapy in cancer. XIAP IN OVARIAN CANCER AND CHEMORESISTANCE C for subsequent analyses.Equal amounts of proteins onto nitrocellulose membranes. To test the changes on cisplatin sensitivity, infected cells were treated with or without cisplatin after a h infection period.The incubation was terminated by the addition of equal Fluoxetine volumes of sample buffer. Data were subjected to one or twoway ANOVA. Construction of recombinant adenovirus and its delivery was carried out as described previously. Attached and detached cells were pooled, pelleted, and resuspended in neutralbuffered formalin. Representative pictures of phasecontrast images are shown.Results represent means SE of three independent experiments.Densitometric analysis for p content are shown on b.Results represent means SE of three independent experiments.B, C cell wholecell lysate was incubated with various concentrations of human recombinant active caspase or caspase of DEVDCHO.In contrast, overexpression of wild type p alone in these p mutants by adenoviral sense cDNA resulted in a concentration. Xiap downregulation significantly increased p content in p mutant reconstituted with wild type p and marked by decreased pinduced p and p MDM levels. These results suggested that caspase activation is necessary, but not sufficient, for the induction of apoptosis in pdeficient cells, and that a functional p may be involved in the completion of the apoptotic process.Alterations in cisplatin cellular retention or excretion, DNA repair mechanism, or apoptotic machinery have been considered important etiological factors in chemoresistance.Xiap has a strong affinity for caspase, a cysteine protease involved in the execution of apoptosis and activity.Thus, removal of the antiapoptotic factor would be expected to have resulted in unleashing of the apoptotic process, probably mediated by the release of caspase from its inhibition.B, synergistic effect of adenoviral wild type p sense expression on apoptosis.These results also suggest that cisplatin resistance may be a multifactorial phenomenon.Results represent means SE of three independent experiments.B, SKOV cells were infected with adenoviral wild type p sense. These findings are, however, consistent with the fact that MDM has caspasesensitive sites. The physiological significance of the observed caspase specificity is not known.MDM is an oncoPregnenolone protein that binds p and facilitates ubiquitinmediated degradation of the tumor suppresser protein. It has been reported that a decrease in MDM content stabilizes p, whereas the opposite is true when the oncoprotein is overexpressed.

Leave a Reply