Abstract 1205: Frequent detection of MDMX isoforms in human ovarian carcinomas

Abstract The p53 tumor suppressor pathway is inactivated in many human tumors either by p53 mutations or through overexpression of negative regulators, such as MDM2 and MDMX. In analogy to MDM2, besides the full-length mRNA several transcript variants, alternatively, as well as, aberrantly spliced transcripts of MDMX have been identified in different tumor cell lines. However, so far there are no studies regarding the expression of MDMX transcript variants in ovarian cancer tissue samples. We therefore screened 34 snap frozen ovarian tumor samples, using a high-temperature First-Strand cDNA synthesis kit to avoid reverse transcriptase artefacts. We identified in addition to MDMX-S numerous new MDMX transcripts in 16 of the 34 tumor samples that were either spliced at genuine exon/intron boundaries or at cryptic splice sites within exons. Furthermore, we could detect the transcript variants MDMX-A and MDMX-XALT2 firstly in ovarian cancer tissue. The MDMX splice variants can be classified into two groups: some isoforms have only retained the p53 binding domain, such as MDMX-S; in contrast, other splice forms consist of an intact C-terminus including the RING-finger domain, such as MDMX-XALT2. In addition, we have analyzed the expression of MDMX splice forms in ovarian cancer cell lines after treatment with chemotherapeutic agent. We observed a significant increase of the MDMX-S splice form while the expression levels of full-length MDMX decreased. This suggests that MDMX splice forms may play a role in mediating chemoresistance by attenuating the p53-pathway. In ongoing studies, we are investigating the role of frequently detected MDMX splice forms regarding their impact on chemoresistance in ovarian cancer in more detail. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1205.