Abstract
BackgroundIt has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of c-IAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer.MethodsWe used semiquantitative RT-PCR assays to analyze 41 cancer and 6 normal tissues. The study included 8 stage I cases; 16 stage II; 17 stageIII; and a control group of 6 samples of normal cervical squamous epithelial tissue.Resultsc-IAP2 and XIAP mRNA levels were similar among the samples, cervical tumors had lower c-IAP1 mRNA levels. Unexpectedly, a clear positive association was found between low levels of XIAP and disease relapse. A log-rank test showed a significant inverse association (p = 0.02) between XIAP expression and tumor aggressiveness, as indicated by disease relapse rates. There were no statistically significant differences in the presence or expression levels of c-IAP1 and c-IAP2 among any of the clinical variables studied. Survivin and its isoforms were undetectable in normal cervical tissues, in contrast with the clear upregulation observed in cancer samples. We found no association between survivin expression and age, clinical stage, histology or menopausal state. Nevertheless, we found that adenocarcinoma tumors expressed higher levels of survivin 2B and DeltaEx3 (p = 0.001 and p = 0.04 respectively, by Kruskal-Wallis). A multivariate Cox's partial likelihood-based analysis showed that only FIGO stage was an independent predictor of outcome.ConclusionThere are no differences in the expression of c-IAP2 and XIAP between normal vs. cancer samples, but XIAP expression correlate in cervical cancer with relapse of this disease in the patients. Otherwise, c-IAP1 was downregulated in the cervical cancer samples. The expression of survivin was upregulated in the patients with cervical cancer. We have found that adenocarcinoma presented higher levels of survivin isoforms 2B and DeltaEx3.
Highlights
It has been shown that inhibitors of apoptosis proteins (IAPs), in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies
No differences were found between XIAP expression and stage, menopause or histology of the tumors (Table 3) a clear association was found between low expression of XIAP and disease relapse (Fig. 2; log-rank p = 0.02)
It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies
Summary
It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of cIAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer. Life and death of cells must be balanced if tissue homeostasis is to be maintained. The main (though not the only) death mechanism by which mammalian cells maintain homeostasis is apoptosis. A group of cysteine proteases, are considered the central executioners of apoptosis. The important role of these proteins in cell death has generated intense research in order to find both positive and negative regulators of their activity. The physiological inhibitors of caspases are a group of antiapoptotic proteins termed IAPs, which are conserved across evolution, with homologues in both vertebrate and invertebrate animal species
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