Predoctoral Fellowships for Students with Disabilities

Rhode Island Hospital, Providence RI

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): CEACAM1 is a cell adhesion molecule. Due to differential splicing two isoforms of CEACAM1 prevail, CEACAM1-4L and CEACAM1-4S. Signaling cascades can commence at or be regulated by cell adhesion molecules that act as receptors. CEACAM1-4L (la) is a multifunctional Ig-like cell adhesion molecule that is lost in a high percentage of carcinomas in the liver, prostate, colon and bladder. Restoration of CEACAM1-4L expression has an inhibitory effect on the tumorgenicity of various types of epithelial cancers but coexpression of the 4S isoform can reverse the inhibitory effects of CEACAM1-4L. These observations suggest that the less well characterized 4S isoform also transduces a signal. A rat hepatoma cell line, 253T, has been developed that does not express CEACAMla or CEACAMlb. These cells have been infected with a retrovirus carrying either the long or the short isoform of CEACAM1. In this model it has been shown that a non-tumorigenic clone of 253T cells (25 3T-IT) becomes tumorigenic when infected with an S form retrovirus (CEACAM1-4S) (lb) but not when infected with an L-form retrovirus or the empty retroviral vector. This model will be used to identify associated proteins involved in the signaling cascades that are activated by the short isoform of CEACAM1 which appears to confer tumorigenicity on 253T-IT cell.