Altered splicing of CEACAM1 in breast cancer: Identification of regulatory sequences that control splicing of CEACAM1 into long or short cytoplasmic domain isoformsReport as inadecuate




Altered splicing of CEACAM1 in breast cancer: Identification of regulatory sequences that control splicing of CEACAM1 into long or short cytoplasmic domain isoforms - Download this document for free, or read online. Document in PDF available to download.

Molecular Cancer

, 7:46

First Online: 28 May 2008Received: 03 January 2008Accepted: 28 May 2008

Abstract

BackgroundCarcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1, a cell adhesion molecule expressed in a variety of cell types is a putative tumor suppressor gene. Alternative splicing of CEACAM1 generates 11 different splice variants, which include 1–4 ectodomains with either short or long cytoplasmic domain generated by the exclusion CEACAM1-S or inclusion CEACAM1-L of exon 7. Studies in rodents indicate that optimal ratios of CEACAM1 splice variants are required to inhibit colonic tumor cell growth.

ResultsWe show that CEACAM1 is expressed in a tissue specific manner with significant differences in the ratios of its short CEACAM1-S and long CEACAM1-L cytoplasmic domain splice variants. Importantly, we find dramatic differences between the ratios of S:L isoforms in normal breast tissues versus breast cancer specimens, suggesting that altered splicing of CEACAM1 may play an important role in tumorogenesis. Furthermore, we have identified two regulatory cis-acting elements required for the alternative splicing of CEACAM1. Replacement of these regulatory elements by human β-globin exon sequences resulted in exon 7-skipped mRNA as the predominant product. Interestingly, while insertion of exon 7 in a β-globin reporter gene resulted in its skipping, exon 7 along with the flanking intron sequences recapitulated the alternative splicing of CEACAM1.

ConclusionOur results indicate that a network of regulatory elements control the alternative splicing of CEACAM1. These findings may have important implications in therapeutic modalities of CEACAM1 linked human diseases.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-7-46 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Author: Shikha Gaur - John E Shively - Yun Yen - Rajesh K Gaur

Source: https://link.springer.com/







Related documents