Abstract 2354: Characterization of three novel splice variants of the RECK tumor and metastasis suppressor gene

Abstract

Abstract REversion-inducing Cysteine-rich protein with Kazal motifs (RECK) encodes a membrane-anchored protein which suppresses both invasion and metastasis by negatively regulating at least three MMP′s, namely: MMP-9, MMP-2 and MT1-MMP. Matrix metalloproteinase (MMP) family members belong to the group of Zn2+ dependent proteolytic enzymes, which are key elements responsible for extracellular matrix (MEC) collapse, being, therefore, directly involved in tumor invasiveness and metastasis. MEC degradation by MMPs not only facilitates tumor invasion, but, also, affects the behavior of tumor and adjacent cells, leading to cancer progression. In general, the relative levels of MMPs increase with tumor progression. Other RECK targets have been identified, such as the extracellular metalloproteinases ADAM10 and CD13/ aminopeptidase N. A positive correlation has been observed between the abundance of RECK expression in tumor samples and better prognosis for patients with gastric, lung, pancreatic and colorectal cancers. Recent studies showed mutations in splicing cis regulatory elements and alterations in the cellular splicing regulatory machinery leading to changes in the splicing pattern of several cancer-related genes, such as CD44, BRCA1, APC, p53 and FHT. In the present study, three novel alternative isoforms of the RECK tumor suppressor gene, namely RECK B (1,548b), RECK D (1,737b) and RECK I (1,101b) were isolated by RT-PCR and their expression profiles were investigated using quantitative real time RT-PCR assays in a normal tissue RNA panel and during human glioma progression. Our results show that RECK isoforms display independent expression patterns when compared to the canonical form, indicating a more complex role for both the canonical and the alternative RECK isoforms in glioma progression. Support: FAPESP, CNPq, FINEP, BNDES, MCT, MS Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2354. doi:10.1158/1538-7445.AM2011-2354